@article{MTMT:34446740, title = {Distinctive features of Zaprionus indianus hemocyte differentiation and function revealed by transcriptomic analysis}, url = {https://m2.mtmt.hu/api/publication/34446740}, author = {Cinege, Gyöngyi Ilona and Magyar, Lilla Brigitta and Kovács, Henrietta and Varga, Viktória and Bodai, László and Zsindely, Nóra and Nagy, Gábor and Hegedűs, Zoltán and Hultmark, Dan and Andó, István}, doi = {10.3389/fimmu.2023.1322381}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {14}, unique-id = {34446740}, issn = {1664-3224}, year = {2023}, eissn = {1664-3224}, orcid-numbers = {Bodai, László/0000-0001-8411-626X; Zsindely, Nóra/0000-0002-6189-3100; Nagy, Gábor/0000-0001-5464-1135; Andó, István/0000-0002-4648-9396} } @article{MTMT:34597768, title = {How to eliminate pathogen without killing oneself? Immunometabolism of encapsulation and melanization in Drosophila}, url = {https://m2.mtmt.hu/api/publication/34597768}, author = {Dolezal, Tomas}, doi = {10.3389/fimmu.2023.1330312}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {14}, unique-id = {34597768}, issn = {1664-3224}, abstract = {Cellular encapsulation associated with melanization is a crucial component of the immune response in insects, particularly against larger pathogens. The infection of a Drosophila larva by parasitoid wasps, like Leptopilina boulardi, is the most extensively studied example. In this case, the encapsulation and melanization of the parasitoid embryo is linked to the activation of plasmatocytes that attach to the surface of the parasitoid. Additionally, the differentiation of lamellocytes that encapsulate the parasitoid, along with crystal cells, is accountable for the melanization process. Encapsulation and melanization lead to the production of toxic molecules that are concentrated in the capsule around the parasitoid and, at the same time, protect the host from this toxic immune response. Thus, cellular encapsulation and melanization represent primarily a metabolic process involving the metabolism of immune cell activation and differentiation, the production of toxic radicals, but also the production of melanin and antioxidants. As such, it has significant implications for host physiology and systemic metabolism. Proper regulation of metabolism within immune cells, as well as at the level of the entire organism, is therefore essential for an efficient immune response and also impacts the health and overall fitness of the organism that survives. The purpose of this "perspective" article is to map what we know about the metabolism of this type of immune response, place it in the context of possible implications for host physiology, and highlight open questions related to the metabolism of this important insect immune response.}, keywords = {encapsulation; ROS; Lamellocyte; Hemocyte; Immunometabolism; melanization; phenoloxidase; Parasitoid wasp}, year = {2023}, eissn = {1664-3224}, orcid-numbers = {Dolezal, Tomas/0000-0001-5217-4465} } @article{MTMT:34298309, title = {Single-cell transcriptomics identifies new blood cell populations in Drosophila released at the onset of metamorphosis}, url = {https://m2.mtmt.hu/api/publication/34298309}, author = {Hirschhaeuser, Alexander and Molitor, Darius and Salinas, Gabriela and Grosshans, Jorg and Rust, Katja and Bogdan, Sven}, doi = {10.1242/dev.201767}, journal-iso = {DEVELOPMENT}, journal = {DEVELOPMENT}, volume = {150}, unique-id = {34298309}, issn = {0950-1991}, abstract = {Drosophila blood cells called hemocytes form an efficient barrier against infections and tissue damage. During metamorphosis, hemocytes undergo tremendous changes in their shape and behavior, preparing them for tissue clearance. Yet, the diversity and functional plasticity of pupal blood cells have not been explored. Here, we combine single-cell transcriptomics and high-resolution microscopy to dissect the heterogeneity and plasticity of pupal hemocytes. We identified undifferentiated and specified hemocytes with different molecular signatures associated with distinct functions such as antimicrobial, antifungal immune defense, cell adhesion or secretion. Strikingly, we identified a highly migratory and immuneresponsive pupal cell population expressing typical markers of the posterior signaling center (PSC), which is known to be an important niche in the larval lymph gland. PSC-like cells become restricted to the abdominal segments and are morphologically very distinct from experiments further suggest that PSC-like cells can transdifferentiate to lamellocytes triggered by parasitoid wasp infestation. In summary, we present the first molecular description of pupal Drosophila blood cells, providing insights into blood cell functional diversification and plasticity during pupal metamorphosis.}, keywords = {BLOOD; DROSOPHILA; HEMOCYTES; MIGRATION; PROGENITOR; PSC; lamellocytes; plasmatocytes; scRNA-seq analysis}, year = {2023}, eissn = {1477-9129}, orcid-numbers = {Molitor, Darius/0000-0001-5998-4014; Grosshans, Jorg/0000-0003-1114-9233; Bogdan, Sven/0000-0002-8753-9855} } @article{MTMT:34162188, title = {Single-cell sequencing of tumor-associated macrophages in a Drosophila model}, url = {https://m2.mtmt.hu/api/publication/34162188}, author = {Khalili, Dilan and Mohammed, Mubasher and Kunc, Martin and Sindlerova, Martina and Ankarklev, Johan and Theopold, Ulrich}, doi = {10.3389/fimmu.2023.1243797}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {14}, unique-id = {34162188}, issn = {1664-3224}, year = {2023}, eissn = {1664-3224} } @article{MTMT:33555087, title = {A Novel Method for Primary Blood Cell Culturing and Selection in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/33555087}, author = {Kúthy-Sutus, Enikő and Kharrat, Bayan and Gábor, Erika and Csordás, Gábor and Sinka, Rita and Honti, Viktor}, doi = {10.3390/cells12010024}, journal-iso = {CELLS-BASEL}, journal = {CELLS}, volume = {12}, unique-id = {33555087}, abstract = {The blood cells of the fruit fly Drosophila melanogaster show many similarities to their vertebrate counterparts, both in their functions and their differentiation. In the past decades, a wide palette of immunological and transgenic tools and methods have been developed to study hematopoiesis in the Drosophila larva. However, the in vivo observation of blood cells is technically restricted by the limited transparency of the body and the difficulty in keeping the organism alive during imaging. Here we describe an improved ex vivo culturing method that allows effective visualization and selection of live blood cells in primary cultures derived from Drosophila larvae. Our results show that cultured hemocytes accurately represent morphological and functional changes following immune challenges and in case of genetic alterations. Since cell culturing has hugely contributed to the understanding of the physiological properties of vertebrate blood cells, this method provides a versatile tool for studying Drosophila hemocyte differentiation and functions ex vivo.}, year = {2023}, eissn = {2073-4409}, orcid-numbers = {Kúthy-Sutus, Enikő/0000-0002-1398-4120; Csordás, Gábor/0000-0001-6871-6839; Sinka, Rita/0000-0003-4040-4184} } @article{MTMT:34110633, title = {Differentiation and function of cardiac valves in the adult Drosophila heart}, url = {https://m2.mtmt.hu/api/publication/34110633}, author = {Meyer, C. and Drechsler, M. and Meyer, H. and Paululat, A.}, doi = {10.1242/jeb.245839}, journal-iso = {J EXP BIOL}, journal = {JOURNAL OF EXPERIMENTAL BIOLOGY}, volume = {226}, unique-id = {34110633}, issn = {0022-0949}, abstract = {Drosophila, like all insects, has an open circulatory system for the distribution of haemolymph and its components. The circulation of the haemolymph is essentially driven by the pumping activity of the linear heart. The heart is constructed as a tube into which the haemolymph is sucked and pumped forward by rhythmic contractions running from the posterior to the anterior, where it leaves the heart tube. The heart harbours cardiac valves to regulate flow directionality, with a single heart valve differentiating during larval development to separate the heart tube into two chambers. During metamorphosis, the heart is partially restructured, with the linear heart tube with one terminal wide-lumen heart chamber being converted into a linear four-chambered heart tube with three valves. As in all metazoan circulatory systems, the cardiac valves play an essential role in regulating the direction of blood flow. We provide evidence that the valves in adult flies arise via transdifferentiation, converting lumen-forming contractile cardiomyocytes into differently structured valve cells. Interestingly, adult cardiac valves exhibit a similar morphology to their larval counterparts, but act differently upon heart beating. Applying calcium imaging in living specimens to analyse activity in valve cells, we show that adult cardiac valves operate owing to muscle contraction. However, valve cell shape dynamics are altered compared with larval valves, which led us to propose our current model of the opening and closing mechanisms in the fly heart. © 2023. Published by The Company of Biologists Ltd.}, keywords = {Animals; DROSOPHILA; DROSOPHILA; animal; Cell Differentiation; Cell Differentiation; physiology; HEART; HEART; Hemodynamics; Hemodynamics; Myocytes, Cardiac; metamorphosis; Heart Valves; heart valve; CARDIOGENESIS; cardiac muscle cell; dorsal vessel; Haemolymph streaming; Heart tube; Valve cells}, year = {2023}, eissn = {1477-9145} } @article{MTMT:33628955, title = {The Drosophila-parasitizing wasp Leptopilina heterotoma: A comprehensive model system in ecology and evolution}, url = {https://m2.mtmt.hu/api/publication/33628955}, author = {Quicray, M. and Wilhelm, L. and Enriquez, T. and He, S. and Scheifler, M. and Visser, B.}, doi = {10.1002/ece3.9625}, journal-iso = {ECOL EVOL}, journal = {ECOLOGY AND EVOLUTION}, volume = {13}, unique-id = {33628955}, issn = {2045-7758}, abstract = {The parasitoid Leptopilina heterotoma has been used as a model system for more than 70 years, contributing greatly to diverse research areas in ecology and evolution. Here, we synthesized the large body of work on L. heterotoma with the aim to identify new research avenues that could be of interest also for researchers studying other parasitoids and insects. We start our review with a description of typical L. heterotoma characteristics, as well as that of the higher taxonomic groups to which this species belongs. We then continue discussing host suitability and immunity, foraging behaviors, as well as fat accumulation and life histories. We subsequently shift our focus towards parasitoid-parasitoid interactions, including L. heterotoma coexistence within the larger guild of Drosophila parasitoids, chemical communication, as well as mating and population structuring. We conclude our review by highlighting the assets of L. heterotoma as a model system, including its intermediate life history syndromes, the ease of observing and collecting natural hosts and wasps, as well as recent genomic advances. © 2023 The Authors. Ecology and Evolution published by John Wiley & Sons Ltd.}, keywords = {LIPIDS; Virulence; fitness; Associative learning; endosymbiont; Sex pheromones; host-parasitoid community}, year = {2023}, eissn = {2045-7758} } @article{MTMT:33809732, title = {The vitellogenin receptor gene contributes to mating and host-searching behaviors in parasitoid wasps}, url = {https://m2.mtmt.hu/api/publication/33809732}, author = {Sheng, Y. and Chen, J. and Jiang, H. and Lu, Y. and Dong, Z. and Pang, L. and Zhang, J. and Wang, Y. and Chen, X. and Huang, J.}, doi = {10.1016/j.isci.2023.106298}, journal-iso = {ISCIENCE}, journal = {ISCIENCE}, volume = {26}, unique-id = {33809732}, abstract = {Vitellogenin receptor (VgR) is essential to vitellogenin uptaking and dominates ovary maturation in insects. However, the function of VgR in parasitoid wasps is largely unknown. Here, we applied the Drosophila parasitoid Leptopilina boulardi as a study model to investigate the function of VgR in parasitoids. Despite the conserved sequence characteristics with other insect VgRs, we found L. boulardi VgR (LbVgR) gene was highly expressed in head but lower in ovary. In addition, we found that LbVgR had no effects on ovary development, but participated in host-searching behavior of female L. boulardi and mating behavior of male L. boulardi. Comparative transcriptome analysis further revealed LbVgR might play crucial roles in regulating the expression of some important chemoreception genes to adjust the parasitoid behaviors. These results will broaden our knowledge of the function of VgR in insects, and contribute to develop advanced pest management strategies using parasitoids as biocontrol agents. © 2023 The Author(s)}, keywords = {developmental biology; CELL BIOLOGY; ETHOLOGY}, year = {2023}, eissn = {2589-0042} } @article{MTMT:34530178, title = {Parasitoid Serpins Evolve Novel Functions to Manipulate Host Homeostasis}, url = {https://m2.mtmt.hu/api/publication/34530178}, author = {Wu, Zhiwei and Yuan, Ruizhong and Gu, Qijuan and Wu, Xiaotong and Gu, Licheng and Ye, Xiqian and Zhou, Yuenan and Huang, Jianhua and Wang, Zhizhi and Chen, Xuexin}, doi = {10.1093/molbev/msad269}, journal-iso = {MOL BIOL EVOL}, journal = {MOLECULAR BIOLOGY AND EVOLUTION}, volume = {40}, unique-id = {34530178}, issn = {0737-4038}, abstract = {Parasitoids introduce various virulence factors when parasitism occurs, and some taxa generate teratocytes to manipulate the host immune system and metabolic homeostasis for the survival and development of their progeny. Host-parasitoid interactions are extremely diverse and complex, yet the evolutionary dynamics are still poorly understood. A category of serpin genes, named CvT-serpins, was discovered to be specifically expressed and secreted by the teratocytes of Cotesia vestalis, an endoparasitoid of the diamondback moth Plutella xylostella. Genomic and phylogenetic analysis indicated that the C. vestalis serpin genes are duplicated and most of them are clustered into 1 monophyletic clade. Intense positive selection was detected at the residues around the P1-P1 ' cleavage sites of the Cv-serpin reactive center loop domain. Functional analyses revealed that, in addition to the conserved function of melanization inhibition (CvT-serpins 1, 16, 18, and 21), CvT-serpins exhibited novel functions, i.e. bacteriostasis (CvT-serpins 3 and 5) and nutrient metabolism regulation (CvT-serpins 8 and 10). When the host-parasitoid system is challenged with foreign bacteria, CvT-serpins act as an immune regulator to reprogram the host immune system through sustained inhibition of host melanization while simultaneously functioning as immune effectors to compensate for this suppression. In addition, we provided evidence that CvT-serpin8 and 10 participate in the regulation of host trehalose and lipid levels by affecting genes involved in these metabolic pathways. These findings illustrate an exquisite tactic by which parasitoids win out in the parasite-host evolutionary arms race by manipulating host immune and nutrition homeostasis via adaptive gene evolution and neofunctionalization.}, keywords = {EXPRESSION; IDENTIFICATION; VENOM; ANTIMICROBIAL ACTIVITY; MULTIPLE SEQUENCE ALIGNMENT; evolutionary biology; SERINE-PROTEASE INHIBITOR; PROPHENOLOXIDASE ACTIVATION; Adaptive evolution; Biochemistry & Molecular Biology; Serpin; Parasitoid wasp; diamondback moth; Pacific white shrimp; Teratocytes; Splicing isoform}, year = {2023}, eissn = {1537-1719}, orcid-numbers = {Huang, Jianhua/0000-0001-6509-1765; Wang, Zhizhi/0000-0003-0189-1741} } @article{MTMT:32876827, title = {Macrophage self-renewal is regulated by transient expression of PDGF- and VEGF-related factor 2}, url = {https://m2.mtmt.hu/api/publication/32876827}, author = {Bakopoulos, D. and Whisstock, J.C. and Warr, C.G. and Johnson, T.K.}, doi = {10.1111/febs.16364}, journal-iso = {FEBS J}, journal = {FEBS JOURNAL}, volume = {289}, unique-id = {32876827}, issn = {1742-464X}, abstract = {Macrophages are an ancient blood cell lineage critical for homeostasis and defence against pathogens. Although their numbers were long thought to be sustained solely by haematopoietic organs, it has recently become clear that their proliferation, or self-renewal, also plays a major role. In the Drosophila larva, macrophages undergo a phase of rapid self-renewal, making this an attractive model for elucidating the signals and regulatory mechanisms involved. However, a central self-renewal pathway has not been identified in this system. Here, we show that the PDGF- and VEGF-receptor related (Pvr) pathway fulfils this role. Our data show that two of the three known Pvr ligands, PDGF- and VEGF-related factor 2 (Pvf2) and Pvf3, are major determinants of overall macrophage numbers, yet they each act in a temporally independent manner and via distinct mechanisms. While Pvf3 is needed prior to the self-renewal period, we find that Pvf2 is critical specifically for expanding the larval macrophage population. We further show that Pvf2 is a potent macrophage mitogen that is kept at limiting quantities by its transient expression in a remarkably small number of blood cells. Together, these data support a novel mechanism for the regulation of macrophage self-renewal rates by the dynamic transcriptional control of Pvf2. Given the strong parallels that exist between Drosophila and vertebrate macrophage systems, it is likely that a similar self-renewal control mechanism is at play across animal phyla. © 2022 Federation of European Biochemical Societies}, year = {2022}, eissn = {1742-4658}, pages = {3735-3751} } @article{MTMT:32915215, title = {Regulating metabolism to shape immune function: Lessons from Drosophila}, url = {https://m2.mtmt.hu/api/publication/32915215}, author = {Bland, M.L.}, doi = {10.1016/j.semcdb.2022.04.002}, journal-iso = {SEMIN CELL DEV BIOL}, journal = {SEMINARS IN CELL & DEVELOPMENTAL BIOLOGY}, unique-id = {32915215}, issn = {1084-9521}, abstract = {Infection with pathogenic microbes is a severe threat that hosts manage by activating the innate immune response. In Drosophila melanogaster, the Toll and Imd signaling pathways are activated by pathogen-associated molecular patterns to initiate cellular and humoral immune processes that neutralize and kill invaders. The Toll and Imd signaling pathways operate in organs such as fat body and gut that control host nutrient metabolism, and infections or genetic activation of Toll and Imd signaling also induce wide-ranging changes in host lipid, carbohydrate and protein metabolism. Metabolic regulation by immune signaling can confer resistance to or tolerance of infection, but it can also lead to pathology and susceptibility to infection. These immunometabolic phenotypes are described in this review, as are changes in endocrine signaling and gene regulation that mediate survival during infection. Future work in the field is anticipated to determine key variables such as sex, dietary nutrients, life stage, and pathogen characteristics that modify immunometabolic phenotypes and, importantly, to uncover the mechanisms used by the immune system to regulate metabolism. © 2022}, keywords = {metabolism; INFECTION; DROSOPHILA; innate immunity}, year = {2022}, eissn = {1096-3634} } @article{MTMT:32915214, title = {Effect of Tachinid Parasitoid Exorista japonica on the Larval Development and Pupation of the Host Silkworm Bombyx mori}, url = {https://m2.mtmt.hu/api/publication/32915214}, author = {Dai, M.-L. and Ye, W.-T. and Jiang, X.-J. and Feng, P. and Zhu, Q.-Y. and Sun, H.-N. and Li, F.-C. and Wei, J. and Li, B.}, doi = {10.3389/fphys.2022.824203}, journal-iso = {FRONT PHYSIOL}, journal = {FRONTIERS IN PHYSIOLOGY}, volume = {13}, unique-id = {32915214}, abstract = {The Tachinidae are natural enemies of many lepidopteran and coleopteran pests of crops, forests, and fruits. However, host-tachinid parasitoid interactions have been largely unexplored. In this study, we investigated the effects of tachinids on host biological traits, using Exorista japonica, a generalist parasitoid, and the silkworm Bombyx mori, its lepidopteran host, as models. We observed that E. japonica parasitoidism did not affect silkworm larval body weight gain and cocooning rate, whereas they caused shortened duration of molting from the final instar to the pupal stage, abnormal molting from larval to pupal stages, and a subsequent decrease in host emergence rate. Moreover, a decrease in juvenile hormone (JH) titer and an increase in 20-hydroxyecdysone (20E) titer in the hemolymph of parasitized silkworms occurred. The transcription of JH and 20E responsive genes was downregulated in mature parasitized hosts, but upregulated in parasitized prepupae while Fushi tarazu factor 1 (Ftz-f1), a nuclear receptor essential in larval ecdysis, showed dramatically reduced expression in parasitized hosts at both the mature and prepupal stages. Moreover, the transcriptional levels of BmFtz-f1 and its downstream target genes encoding cuticle proteins were downregulated in epidermis of parasitized hosts. Meanwhile, the content of trehalose was decreased in the hemolymph, while chitin content in the epidermis was increased in parasitized silkworm prepupae. These data reveal that the host may fine-tune JH and 20E synthesis to shorten developmental duration to combat established E. japonica infestation, while E. japonica silences BmFtz-f1 transcription to inhibit host pupation. This discovery highlights the novel target mechanism of tachinid parasitoids and provides new clues to host/tachinid parasitoid relationships. Copyright © 2022 Dai, Ye, Jiang, Feng, Zhu, Sun, Li, Wei and Li.}, keywords = {Bombyx mori; Ftz-F1; 20E signaling; pupation metamorphosis; tachinid parasitoid}, year = {2022}, eissn = {1664-042X} } @article{MTMT:32915213, title = {Injury-induced inflammatory signaling and hematopoiesis in Drosophila}, url = {https://m2.mtmt.hu/api/publication/32915213}, author = {Evans, C.J. and Liu, T. and Girard, J.R. and Banerjee, U.}, doi = {10.1073/pnas.2119109119}, journal-iso = {P NATL ACAD SCI USA}, journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, volume = {119}, unique-id = {32915213}, issn = {0027-8424}, abstract = {Inflammatory response in Drosophila to sterile (axenic) injury in embryos and adults has received some attention in recent years, and most concentrate on the events at the injury site. Here we focus on the effect sterile injury has on the hematopoietic organ, the lymph gland, and the circulating blood cells in the larva, the developmental stage at which major events of hematopoiesis are evident. In mammals, injury activates Toll-like receptor/NF-κB signaling in macrophages, which then express and secrete secondary, proinflammatory cytokines. In Drosophila larvae, distal puncture injury of the body wall epidermis causes a rapid activation of Toll and Jun kinase (JNK) signaling throughout the hematopoietic system and the differentiation of a unique blood cell type, the lamellocyte. Furthermore, we find that Toll and JNK signaling are coupled in their activation. Secondary to this Toll/JNK response, a cytokine, Upd3, is induced as a Toll pathway transcriptional target, which then promotes JAK/STAT signaling within the blood cells. Toll and JAK/STAT signaling are required for the emergence of the injury-induced lamellocytes. This is akin to the derivation of specialized macrophages in mammalian systems. Upstream, at the injury site, a Duox-@@@@@and peroxide-dependent signal causes the activation of the proteases Grass and SPE, needed for the activation of the Toll-ligand Spz, but microbial sensors or the proteases most closely associated with them during septic injury are not involved in the axenic inflammatory response. Copyright © 2022 the Author(s).}, keywords = {Animals; Adult; Inflammation; Inflammation; Inflammation; metabolism; BLOOD; GENETICS; ARTICLE; signal transduction; signal transduction; signal transduction; DROSOPHILA; DROSOPHILA; toll like receptor; cytokine; cytokine; animal; Cell Differentiation; MACROPHAGE; controlled study; nonhuman; animal tissue; animal cell; developmental stage; quantitative analysis; mammal; enzyme activation; embryo; hydrogen peroxide; protein expression; protein targeting; stress activated protein kinase; MAMMALS; immunoglobulin enhancer binding protein; cytokine release; real time polymerase chain reaction; STAT protein; Janus kinase; Hematopoiesis; Hematopoiesis; Hematopoiesis; penetrating trauma; Drosophila Proteins; Wasps; hematopoietic system; Drosophila protein; WASP; wound; insect larva; Toll/TLR}, year = {2022}, eissn = {1091-6490} } @article{MTMT:33318026, title = {Mutagenesis of both prophenoloxidases in the fall armyworm induces major defects in metamorphosis}, url = {https://m2.mtmt.hu/api/publication/33318026}, author = {Eychenne, Magali and Girard, Pierre-Alain and Frayssinet, Marie and Lan, Laijiao and Pages, Sylvie and Duvic, Bernard and Negre, Nicolas}, journal-iso = {J INSECT PHYSIOL}, journal = {JOURNAL OF INSECT PHYSIOLOGY}, volume = {139}, unique-id = {33318026}, issn = {0022-1910}, abstract = {Upon infection, the phenoloxidase system in arthropods is rapidly mobilized and constitutes a major defense system against invaders. The activation of the key enzymes prophenoloxidase (PPO) and their action in immunity through melanization and encapsulation of foreign bodies in hemolymph has been described in many insects. On the other hand, little is known about PPOs involvement in other essential functions related to insect development. In this paper, we investigated the function of the two PPOs of the crop pest, Spodoptera frugiperda (PPO1 and PPO2). We show that PPOs are mainly expressed in hemocytes with the PPO2 expressed at higher levels than the PPO1. In addition, these two genes are expressed in the same tissue and at the same stages of insect development. Through the generation of loss-of-function mutants by CRISPR/Cas9 method, we show that the presence of PPOs is essential for the normal development of the pupa and the survival of the insect.}, keywords = {Development; LEPIDOPTERA; CRISPR; melanization; phenoloxidase; fall armyworm; Spodoptera frugiperda}, year = {2022}, eissn = {1879-1611}, pages = {4399-4399} } @article{MTMT:33178825, title = {Irradiation and parasitism affect the ability of larval hemocytes of Anastrepha obliqua for phagocytosis and the production of reactive oxygen species}, url = {https://m2.mtmt.hu/api/publication/33178825}, author = {Gomez-Alonso, Itzia and Baltierra-Uribe, Shantal and Sanchez-Torres, Luvia and Cancino-Diaz, Mario and Cancino-Diaz, Juan and Rodriguez-Martinez, Sandra and Ovruski, Sergio M. and Hendrichs, Jorge and Cancino, Jorge}, doi = {10.1002/arch.21953}, journal-iso = {ARCH INSECT BIOCHEM}, journal = {ARCHIVES OF INSECT BIOCHEMISTRY AND PHYSIOLOGY}, unique-id = {33178825}, issn = {0739-4462}, abstract = {The development of the parasitoid Doryctobracon crawfordi (Viereck) (Hymenoptera: Braconidae) in Anastrepha obliqua (McQuart) (Diptera: Tephritidae) larvae is unviable in nature; however, if the host larva is irradiated at 160 Gy, the parasitoid develops and emerges successfully. This suggests that radiation affects the immune responses of A. obliqua larvae, while the underlying mechanisms remain to be revealed. Using optical and electronic microscopies we determined the number and type of hemocyte populations found inside the A. obliqua larvae, either nonirradiated, irradiated at 160 Gy, parasitized by D. crawfordi, or irradiated and parasitized. Based on flow cytometry, the capacity to produce reactive oxygen species (ROS) was determined by the 123-dihydrorhodamine method in those hemocyte cells. Five cell populations were found in the hemolymph of A. obliqua larvae, two of which (granulocytes and plasmatocytes) can phagocytize and produce ROS. A reduction in the number of cells, mainly of the phagocytic type, was observed, as well as the capacity of these cells to produce ROS, when A. obliqua larvae were irradiated. Both radiation and parasitization decreased the ROS production, and when A. obliqua larvae were irradiated followed by parasitization by D. crawfordi, the reduction of the ROS level was even greater. In contrast, a slight increase in the size of these cells was observed in the hemolymph of the parasitized larvae compared to those in nonparasitized larvae. These results suggest that radiation significantly affects the phagocytic cells of A. obliqua and thus permits the development of the parasitoid D. crawfordi.}, keywords = {PHAGOCYTOSIS; Flow Cytometry; Reactive oxygen species; immune responses; host radiation}, year = {2022}, eissn = {1520-6327} } @article{MTMT:33039275, title = {Hematopoietic plasticity mapped in Drosophila and other insects}, url = {https://m2.mtmt.hu/api/publication/33039275}, author = {Hultmark, Dan and Andó, István}, doi = {10.7554/eLife.78906}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {11}, unique-id = {33039275}, issn = {2050-084X}, year = {2022}, eissn = {2050-084X}, orcid-numbers = {Hultmark, Dan/0000-0002-6506-5855; Andó, István/0000-0002-4648-9396} } @article{MTMT:33050458, title = {Peeling Back the Layers of Lymph Gland Structure and Regulation}, url = {https://m2.mtmt.hu/api/publication/33050458}, author = {Kharrat, Bayan and Csordás, Gábor and Honti, Viktor}, doi = {10.3390/ijms23147767}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {23}, unique-id = {33050458}, issn = {1661-6596}, abstract = {During the past 60 years, the fruit fly, Drosophila melanogaster, has proven to be an excellent model to study the regulation of hematopoiesis. This is not only due to the evolutionarily conserved signalling pathways and transcription factors contributing to blood cell fate, but also to convergent evolution that led to functional similarities in distinct species. An example of convergence is the compartmentalization of blood cells, which ensures the quiescence of hematopoietic stem cells and allows for the rapid reaction of the immune system upon challenges. The lymph gland, a widely studied hematopoietic organ of the Drosophila larva, represents a microenvironment with similar features and functions to classical hematopoietic stem cell niches of vertebrates. Lymph gland studies were effectively supported by the unparalleled toolkit developed in Drosophila, which enabled the high-resolution investigation of the cellular composition and regulatory interaction networks of the lymph gland. In this review, we summarize how our understanding of lymph gland structure and hematopoietic cell-to-cell communication evolved during the past decades and compare their analogous features to those of the vertebrate hematopoietic stem cell niche.}, keywords = {IMMUNE-RESPONSE; DROSOPHILA; matrix protein; Hematopoiesis; SELF-RENEWAL; HEMATOPOIETIC STEM-CELL; Biochemistry & Molecular Biology; HSC; N-cadherin; lymph gland; EMBRYONIC ORIGIN; Drosophila larvae; PROGENITOR MAINTENANCE; HEMOCYTE LINEAGES}, year = {2022}, eissn = {1422-0067}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839} } @article{MTMT:33318025, title = {NEURON-MACROPHAGE INTERACTIONS IN MODELS OF CHEMOTHERAPY-INDUCED PERIPHERAL NEUROPATHY}, url = {https://m2.mtmt.hu/api/publication/33318025}, author = {Smith, Madison and Hammond, Luke and Grueber, Wesley and Shin, Grace}, journal-iso = {J PERIPHER NERV SYST}, journal = {JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM}, volume = {27}, unique-id = {33318025}, issn = {1085-9489}, keywords = {Inflammation; MACROPHAGES; DROSOPHILA; PACLITAXEL; chemotherapy-induced peripheral neuropathy}, year = {2022}, eissn = {1529-8027}, pages = {S123-S124} } @article{MTMT:32876692, title = {Adaptations and counter-adaptations in Drosophila host–parasitoid interactions: advances in the molecular mechanisms}, url = {https://m2.mtmt.hu/api/publication/32876692}, author = {Wertheim, B.}, doi = {10.1016/j.cois.2022.100896}, journal-iso = {CURR OPIN INSECT SCI}, journal = {CURRENT OPINION IN INSECT SCIENCE}, volume = {51}, unique-id = {32876692}, issn = {2214-5745}, abstract = {Both hosts and parasitoids evolved a diverse array of traits and strategies for their antagonistic interactions, affecting their chances of encounter, attack and survival after parasitoid attack. This review summarizes the recent progress that has been made in elucidating the molecular mechanisms of these adaptations and counter-adaptations in various Drosophila host–parasitoid interactions. For the hosts, it focuses on the neurobiological and genetic control of strategies in Drosophila adults and larvae of avoidance or escape behaviours upon sensing the parasitoids, and the immunological defences involving diverse classes of haemocytes. For the parasitoids, it highlights their behavioural strategies in host finding, as well as the rich variety of venom components that evolved and were partially acquired through horizontal gene transfer. Recent studies revealed the mechanisms by which these venom components manipulate their parasitized hosts in exhibiting escape behaviour to avoid superparasitism, and their counter-strategies to evade or obstruct the hosts’ immunological defences. © 2022 The Author(s)}, year = {2022}, eissn = {2214-5753} } @article{MTMT:32972124, title = {The Dual Functions of a Bracovirus C-Type Lectin in Caterpillar Immune Response Manipulation}, url = {https://m2.mtmt.hu/api/publication/32972124}, author = {Wu, Xiaotong and Wu, Zhiwei and Ye, Xiqian and Pang, Lan and Sheng, Yifeng and Wang, Zehua and Zhou, Yuenan and Zhu, Jiachen and Hu, Rongmin and Zhou, Sicong and Chen, Jiani and Wang, Zhizhi and Shi, Min and Huang, Jianhua and Chen, Xuexin}, doi = {10.3389/fimmu.2022.877027}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {13}, unique-id = {32972124}, issn = {1664-3224}, abstract = {Parasitoids are widespread in natural ecosystems and normally equipped with diverse viral factors to defeat host immune responses. On the other hand, parasitoids can enhance the antibacterial abilities and improve the hypoimmunity traits of parasitized hosts that may encounter pathogenic infections. These adaptive strategies guarantee the survival of parasitoid offspring, yet their underlying mechanisms are poorly understood. Here, we focused on Cotesia vestalis, an endoparasitoid of the diamondback moth Plutella xylostella, and found that C. vestalis parasitization decreases the number of host hemocytes, leading to disruption of the encapsulation reaction. We further found that one bracovirus C-type lectin gene, CvBV_28-1, is highly expressed in the hemocytes of parasitized hosts and participates in suppressing the proliferation rate of host hemocytes, which in turn reduces their population and represses the process of encapsulation. Moreover, CvBV_28-1 presents a classical bacterial clearance ability via the agglutination response in a Ca2+-dependent manner in response to gram-positive bacteria. Our study provides insights into the innovative strategy of a parasitoid-derived viral gene that has dual functions to manipulate host immunity for a successful parasitism.}, keywords = {C-TYPE LECTIN; immunosuppression; Hypoimmunity; agglutination; bracovirus; hemocytes proliferation}, year = {2022}, eissn = {1664-3224} } @article{MTMT:33041863, title = {Drosophila Innate Immunity Involves Multiple Signaling Pathways and Coordinated Communication Between Different Tissues}, url = {https://m2.mtmt.hu/api/publication/33041863}, author = {Yu, S. and Luo, F. and Xu, Y. and Zhang, Y. and Jin, L.H.}, doi = {10.3389/fimmu.2022.905370}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {13}, unique-id = {33041863}, issn = {1664-3224}, abstract = {The innate immune response provides the first line of defense against invading pathogens, and immune disorders cause a variety of diseases. The fruit fly Drosophila melanogaster employs multiple innate immune reactions to resist infection. First, epithelial tissues function as physical barriers to prevent pathogen invasion. In addition, macrophage-like plasmatocytes eliminate intruders through phagocytosis, and lamellocytes encapsulate large particles, such as wasp eggs, that cannot be phagocytosed. Regarding humoral immune responses, the fat body, equivalent to the mammalian liver, secretes antimicrobial peptides into hemolymph, killing bacteria and fungi. Drosophila has been shown to be a powerful in vivo model for studying the mechanism of innate immunity and host-pathogen interactions because Drosophila and higher organisms share conserved signaling pathways and factors. Moreover, the ease with which Drosophila genetic and physiological characteristics can be manipulated prevents interference by adaptive immunity. In this review, we discuss the signaling pathways activated in Drosophila innate immunity, namely, the Toll, Imd, JNK, JAK/STAT pathways, and other factors, as well as relevant regulatory networks. We also review the mechanisms by which different tissues, including hemocytes, the fat body, the lymph gland, muscles, the gut and the brain coordinate innate immune responses. Furthermore, the latest studies in this field are outlined in this review. In summary, understanding the mechanism underlying innate immunity orchestration in Drosophila will help us better study human innate immunity-related diseases. Copyright © 2022 Yu, Luo, Xu, Zhang and Jin.}, keywords = {DROSOPHILA; innate immunity; immune response; SIGNALING PATHWAY; Tissue communication}, year = {2022}, eissn = {1664-3224} } @article{MTMT:33318023, title = {Parasite reliance on its host gut microbiota for nutrition and survival}, url = {https://m2.mtmt.hu/api/publication/33318023}, author = {Zhou, Sicong and Lu, Yueqi and Chen, Jiani and Pan, Zhongqiu and Pang, Lan and Wang, Ying and Zhang, Qichao and Strand, Michael R. and Chen, Xue-Xin and Huang, Jianhua}, doi = {10.1038/s41396-022-01301-z}, journal-iso = {ISME J}, journal = {ISME JOURNAL}, volume = {16}, unique-id = {33318023}, issn = {1751-7362}, abstract = {Studying the microbial symbionts of eukaryotic hosts has revealed a range of interactions that benefit host biology. Most eukaryotes are also infected by parasites that adversely affect host biology for their own benefit. However, it is largely unclear whether the ability of parasites to develop in hosts also depends on host-associated symbionts, e.g., the gut microbiota. Here, we studied the parasitic wasp Leptopilina boulardi (Lb) and its host Drosophila melanogaster. Results showed that Lb successfully develops in conventional hosts (CN) with a gut microbiota but fails to develop in axenic hosts (AX) without a gut microbiota. We determined that developing Lb larvae consume fat body cells that store lipids. We also determined that much larger amounts of lipid accumulate in fat body cells of parasitized CN hosts than parasitized AX hosts. CN hosts parasitized by Lb exhibited large increases in the abundance of the bacterium Acetobacter pomorum in the gut, but did not affect the abundance of Lactobacillus fructivorans which is another common member of the host gut microbiota. However, AX hosts inoculated with A. pomorum and/or L. fructivorans did not rescue development of Lb. In contrast, AX larvae inoculated with A. pomorum plus other identified gut community members including a Bacillus sp. substantially rescued Lb development. Rescue was further associated with increased lipid accumulation in host fat body cells. Insulin-like peptides increased in brain neurosecretory cells of parasitized CN larvae. Lipid accumulation in the fat body of CN hosts was further associated with reduced Bmm lipase activity mediated by insulin/insulin-like growth factor signaling (IIS). Altogether, our results identify a previously unknown role for the gut microbiota in defining host permissiveness for a parasite. Our findings also identify a new paradigm for parasite manipulation of host metabolism that depends on insulin signaling and the gut microbiota.}, year = {2022}, eissn = {1751-7370}, pages = {2574-2586}, orcid-numbers = {Chen, Jiani/0000-0003-3161-8519; Huang, Jianhua/0000-0001-6509-1765} } @article{MTMT:31940120, title = {Immunoprofiling of Drosophila Hemocytes by Single-cell Mass Cytometry}, url = {https://m2.mtmt.hu/api/publication/31940120}, author = {Balog, József Ágoston and Honti, Viktor and Kurucz, Judit Éva and Kari, Beáta and Puskás, László and Andó, István and Szebeni, Gábor}, doi = {10.1016/j.gpb.2020.06.022}, journal-iso = {GENOM PROTEOM BIOINF}, journal = {GENOMICS PROTEOMICS & BIOINFORMATICS}, volume = {19}, unique-id = {31940120}, issn = {1672-0229}, year = {2021}, eissn = {2210-3244}, pages = {243-252}, orcid-numbers = {Andó, István/0000-0002-4648-9396; Szebeni, Gábor/0000-0002-6998-5632} } @article{MTMT:32426748, title = {Neofunctionalization of an ancient domain allows parasites to avoid intraspecific competition by manipulating host behaviour}, url = {https://m2.mtmt.hu/api/publication/32426748}, author = {Chen, Jiani and Fang, Gangqi and Pang, Lan and Sheng, Yifeng and Zhang, Qichao and Zhou, Yuenan and Zhou, Sicong and Lu, Yueqi and Liu, Zhiguo and Zhang, Yixiang and Li, Guiyun and Shi, Min and Chen, Xuexin and Zhan, Shuai and Huang, Jianhua}, doi = {10.1038/s41467-021-25727-9}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {12}, unique-id = {32426748}, issn = {2041-1723}, abstract = {Intraspecific competition is a major force in mediating population dynamics, fuelling adaptation, and potentially leading to evolutionary diversification. Among the evolutionary arms races between parasites, one of the most fundamental and intriguing behavioural adaptations and counter-adaptations are superparasitism and superparasitism avoidance. However, the underlying mechanisms and ecological contexts of these phenomena remain underexplored. Here, we apply the Drosophila parasite Leptopilina boulardi as a study system and find that this solitary endoparasitic wasp provokes a host escape response for superparasitism avoidance. We combine multi-omics and in vivo functional studies to characterize a small set of RhoGAP domain-containing genes that mediate the parasite's manipulation of host escape behaviour by inducing reactive oxygen species in the host central nervous system. We further uncover an evolutionary scenario in which neofunctionalization and specialization gave rise to the novel role of RhoGAP domain in avoiding superparasitism, with an ancestral origin prior to the divergence between Leptopilina specialist and generalist species. Our study suggests that superparasitism avoidance is adaptive for a parasite and adds to our understanding of how the molecular manipulation of host behaviour has evolved in this system.Evolutionary arms races can drive adaptations in hosts and parasites as well as among competing parasites. A combination of multi-omics and functional tests identifies a set of genes that allow a parasitic wasp to minimize intraspecific competition by inducing hosts to escape before more wasps can parasitize them.}, year = {2021}, eissn = {2041-1723} } @article{MTMT:32361808, title = {Identification of functionally distinct macrophage subpopulations in Drosophila}, url = {https://m2.mtmt.hu/api/publication/32361808}, author = {Coates, Jonathon Alexis and Brooks, Elliot and Brittle, Amy Louise and Armitage, Emma Louise and Zeidler, Martin Peter and Evans, Iwan Robert}, doi = {10.7554/eLife.58686}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {10}, unique-id = {32361808}, issn = {2050-084X}, abstract = {Vertebrate macrophages are a highly heterogeneous cell population, but while Drosophila blood is dominated by a macrophage-like lineage (plasmatocytes), until very recently these cells were considered to represent a homogeneous population. Here, we present our identification of enhancer elements labelling plasmatocyte subpopulations, which vary in abundance across development. These subpopulations exhibit functional differences compared to the overall population, including more potent injury responses and differential localisation and dynamics in pupae and adults. Our enhancer analysis identified candidate genes regulating plasmatocyte behaviour: pan-plasmatocyte expression of one such gene (Calnexin14D) improves wound responses, causing the overall population to resemble more closely the subpopulation marked by the Calnexin14D-associated enhancer. Finally, we show that exposure to increased levels of apoptotic cell death modulates subpopulation cell numbers. Taken together this demonstrates macrophage heterogeneity in Drosophila, identifies mechanisms involved in subpopulation specification and function and facilitates the use of Drosophila to study macrophage heterogeneity in vivo.}, year = {2021}, eissn = {2050-084X} } @article{MTMT:31743832, title = {There and back again: The mechanisms of differentiation and transdifferentiation in Drosophila blood cells}, url = {https://m2.mtmt.hu/api/publication/31743832}, author = {Csordás, Gábor and Gábor, Erika and Honti, Viktor}, doi = {10.1016/j.ydbio.2020.10.006}, journal-iso = {DEV BIOL}, journal = {DEVELOPMENTAL BIOLOGY}, volume = {469}, unique-id = {31743832}, issn = {0012-1606}, year = {2021}, eissn = {1095-564X}, pages = {135-143}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839} } @article{MTMT:32361576, title = {Haemocyte-mediated immunity in insects: Cells, processes and associated components in the fight against pathogens and parasites}, url = {https://m2.mtmt.hu/api/publication/32361576}, author = {Eleftherianos, Ioannis and Heryanto, Christa and Bassal, Taha and Zhang, Wei and Tettamanti, Gianluca and Mohamed, Amr}, doi = {10.1111/imm.13390}, journal-iso = {IMMUNOLOGY}, journal = {IMMUNOLOGY}, volume = {164}, unique-id = {32361576}, issn = {0019-2805}, abstract = {The host defence of insects includes a combination of cellular and humoral responses. The cellular arm of the insect innate immune system includes mechanisms that are directly mediated by haemocytes (e.g., phagocytosis, nodulation and encapsulation). In addition, melanization accompanying coagulation, clot formation and wound healing, nodulation and encapsulation processes leads to the formation of cytotoxic redox-cycling melanin precursors and reactive oxygen and nitrogen species. However, demarcation between cellular and humoral immune reactions as two distinct categories is not straightforward. This is because many humoral factors affect haemocyte functions and haemocytes themselves are an important source of many humoral molecules. There is also a considerable overlap between cellular and humoral immune functions that span from recognition of foreign intruders to clot formation. Here, we review these immune reactions starting with the cellular mechanisms that limit haemolymph loss and participate in wound healing and clot formation and advancing to cellular functions that are critical in restricting pathogen movement and replication. This information is important because it highlights that insect cellular immunity is controlled by a multilayered system, different components of which are activated by different pathogens or during the different stages of the infection.}, keywords = {haematopoiesis; haemocytes; prophenoloxidase; autophagy and apoptosis; cytotoxic intermediates; insect cellular immunity}, year = {2021}, eissn = {1365-2567}, pages = {401-432}, orcid-numbers = {Eleftherianos, Ioannis/0000-0002-4822-3110; Mohamed, Amr/0000-0003-2788-5534} } @article{MTMT:31867767, title = {Comparative hematopoiesis and signal transduction in model organisms}, url = {https://m2.mtmt.hu/api/publication/31867767}, author = {Gautam, D.K. and Chimata, A.V. and Gutti, R.K. and Paddibhatla, I.}, doi = {10.1002/jcp.30287}, journal-iso = {J CELL PHYSIOL}, journal = {JOURNAL OF CELLULAR PHYSIOLOGY}, volume = {236}, unique-id = {31867767}, issn = {0021-9541}, abstract = {Hematopoiesis is a continuous phenomenon involving the formation of hematopoietic stem cells (HSCs) giving rise to diverse functional blood cells. This developmental process of hematopoiesis is evolutionarily conserved, yet comparably different in various model organisms. Vertebrate HSCs give rise to all types of mature cells of both the myeloid and the lymphoid lineages sequentially colonizing in different anatomical tissues. Signal transduction in HSCs facilitates their potency and specifies branching of lineages. Understanding the hematopoietic signaling pathways is crucial to gain insights into their deregulation in several blood-related disorders. The focus of the review is on hematopoiesis corresponding to different model organisms and pivotal role of indispensable hematopoietic pathways. We summarize and discuss the fundamentals of blood formation in both invertebrate and vertebrates, examining the requirement of key signaling nexus in hematopoiesis. Knowledge obtained from such comparative studies associated with developmental dynamics of hematopoiesis is beneficial to explore the therapeutic options for hematopoietic diseases. © 2021 Wiley Periodicals LLC}, keywords = {BLOOD; MICE; ZEBRAFISH; DROSOPHILA; human; signaling; Hematopoiesis; MODEL ORGANISM}, year = {2021}, eissn = {1097-4652}, pages = {5592-5619} } @article{MTMT:32913576, title = {CK1α protects WAVE from degradation to regulate cell shape and motility in the immune response}, url = {https://m2.mtmt.hu/api/publication/32913576}, author = {Hirschhäuser, A. and van, Cann M. and Bogdan, S.}, doi = {10.1242/jcs.258891}, journal-iso = {J CELL SCI}, journal = {JOURNAL OF CELL SCIENCE}, volume = {134}, unique-id = {32913576}, issn = {0021-9533}, abstract = {The WAVE regulatory complex (WRC) is the main activator of the Arp2/3 complex, promoting lamellipodial protrusions in migrating cells. The WRC is basally inactive but can be activated by Rac1 and phospholipids, and through phosphorylation. However, the in vivo relevance of the phosphorylation of WAVE proteins remains largely unknown. Here, we identified casein kinase I alpha (CK1α) as a regulator of WAVE, thereby controlling cell shape and cell motility in Drosophila macrophages. CK1α binds and phosphorylates WAVE in vitro. Phosphorylation of WAVE by CK1α appears not to be required for activation but, rather, regulates its stability. Pharmacologic inhibition of CK1α promotes ubiquitin-dependent degradation of WAVE. Consistently, loss of Ck1α but not ck2 function phenocopies the depletion of WAVE. Phosphorylation-deficient mutations in the CK1α consensus sequences within the VCA domain of WAVE can neither rescue mutant lethality nor lamellipodium defects. By contrast, phosphomimetic mutations rescue all cellular and developmental defects. Finally, RNAi-mediated suppression of 26S proteasome or E3 ligase complexes substantially rescues lamellipodia defects in CK1α-depleted macrophages. Therefore, we conclude that basal phosphorylation of WAVE by CK1α protects it from premature ubiquitin-dependent degradation, thus promoting WAVE function in vivo. © 2021. Published by The Company of Biologists Ltd}, keywords = {Humans; PHOSPHORYLATION; PHOSPHORYLATION; PHOSPHORYLATION; metabolism; MACROPHAGES; GENETICS; DROSOPHILA; human; Immunity; Immunity; ACTIN; cell migration; WAVE; Cell Shape; Cell Shape; Cell Shape; cell motility; Wiskott Aldrich syndrome protein; Arp2/3; Lamellipodia; CK2; casein kinase Ialpha; casein kinase Ialpha; CK1α; Ubiquitin-dependent protein degradation; Wiskott-Aldrich Syndrome Protein Family}, year = {2021}, eissn = {1477-9137} } @article{MTMT:31871704, title = {Two novel venom proteins underlie divergent parasitic strategies between a generalist and a specialist parasite}, url = {https://m2.mtmt.hu/api/publication/31871704}, author = {Huang, J. and Chen, J. and Fang, G. and Pang, L. and Zhou, S. and Zhou, Y. and Pan, Z. and Zhang, Q. and Sheng, Y. and Lu, Y. and Liu, Z. and Zhang, Y. and Li, G. and Shi, M. and Chen, X. and Zhan, S.}, doi = {10.1038/s41467-020-20332-8}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {12}, unique-id = {31871704}, issn = {2041-1723}, abstract = {Parasitoids are ubiquitous in natural ecosystems. Parasitic strategies are highly diverse among parasitoid species, yet their underlying genetic bases are poorly understood. Here, we focus on the divergent adaptation of a specialist and a generalist drosophilid parasitoids. We find that a novel protein (Lar) enables active immune suppression by lysing the host lymph glands, eventually leading to successful parasitism by the generalist. Meanwhile, another novel protein (Warm) contributes to a passive strategy by attaching the laid eggs to the gut and other organs of the host, leading to incomplete encapsulation and helping the specialist escape the host immune response. We find that these diverse parasitic strategies both originated from lateral gene transfer, followed with duplication and specialization, and that they might contribute to the shift in host ranges between parasitoids. Our results increase our understanding of how novel gene functions originate and how they contribute to host adaptation. © 2021, The Author(s).}, keywords = {Animals; Male; Male; metabolism; PROTEIN; GENETICS; ARTICLE; EVOLUTION; VENOM; HOST SPECIFICITY; PHYLOGENY; PHYLOGENY; DROSOPHILA; DROSOPHILA; immunology; animal; Chemistry; ADAPTATION; physiology; nonhuman; Host-Parasite Interactions; Species Specificity; Immunity; Immunity; Parasitism; host parasite interaction; parasite; parasite; species difference; parasitology; unclassified drug; encapsulation; immune response; protein domain; PARASITES; fly; mucin; gene function; Animal Structures; Animal Structures; specialist; Wasps; host range; Parasitoid; Parasitoid; WASP; Genome, Insect; Protein Domains; insect protein; Insect Proteins; generalist; Mucins; Host adaptation; Drosophilidae; insect genome; Leptopilina; protein lar; protein warm}, year = {2021}, eissn = {2041-1723} } @article{MTMT:32587143, title = {Proteasome α6 Subunit Negatively Regulates the JAK/STAT Pathway and Blood Cell Activation in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/32587143}, author = {Järvelä-Stölting, M. and Vesala, L. and Maasdorp, M.K. and Ciantar, J. and Rämet, M. and Valanne, S.}, doi = {10.3389/fimmu.2021.729631}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {12}, unique-id = {32587143}, issn = {1664-3224}, abstract = {JAK/STAT signaling regulates central biological functions such as development, cell differentiation and immune responses. In Drosophila, misregulated JAK/STAT signaling in blood cells (hemocytes) induces their aberrant activation. Using mass spectrometry to analyze proteins associated with a negative regulator of the JAK/STAT pathway, and by performing a genome-wide RNAi screen, we identified several components of the proteasome complex as negative regulators of JAK/STAT signaling in Drosophila. A selected proteasome component, Prosα6, was studied further. In S2 cells, Prosα6 silencing decreased the amount of the known negative regulator of the pathway, ET, leading to enhanced expression of a JAK/STAT pathway reporter gene. Silencing of Prosα6 in vivo resulted in activation of the JAK/STAT pathway, leading to the formation of lamellocytes, a specific hemocyte type indicative of hemocyte activation. This hemocyte phenotype could be partially rescued by simultaneous knockdown of either the Drosophila STAT transcription factor, or MAPKK in the JNK-pathway. Our results suggest a role for the proteasome complex components in the JAK/STAT pathway in Drosophila blood cells both in vitro and in vivo. Copyright © 2021 Järvelä-Stölting, Vesala, Maasdorp, Ciantar, Rämet and Valanne.}, keywords = {RNA Interference; Drosophila melanogaster; Lamellocyte; Hemocyte; Fruit fly; JAK/STAT PATHWAY; Eye Transformer; the proteasome complex}, year = {2021}, eissn = {1664-3224} } @article{MTMT:32006424, title = {A population genomic investigation of immune cell diversity and phagocytic capacity in a butterfly}, url = {https://m2.mtmt.hu/api/publication/32006424}, author = {Keehnen, N.L.P. and Fors, L. and Järver, P. and Spetz, A.-L. and Nylin, S. and Theopold, U. and Wheat, C.W.}, doi = {10.3390/genes12020279}, journal-iso = {GENES-BASEL}, journal = {GENES}, volume = {12}, unique-id = {32006424}, issn = {2073-4425}, abstract = {Insects rely on their innate immune system to successfully mediate complex interactions with their internal microbiota, as well as the microbes present in the environment. Given the variation in microbes across habitats, the challenges to respond to them are likely to result in local adaptations in the immune system. Here we focus upon phagocytosis, a mechanism by which pathogens and foreign particles are engulfed in order to be contained, killed, and processed. We investigated the phenotypic and genetic variation related to phagocytosis in two allopatric populations of the butterfly Pieris napi. Populations were found to differ in their hemocyte composition and overall phagocytic capability, driven by the increased phagocytic propensity of each cell type. Yet, genes annotated to phagocytosis showed no large genomic signal of divergence. However, a gene set enrichment analysis on significantly divergent genes identified loci involved in glutamine metabolism, which recently have been linked to immune cell differentiation in mammals. Together these results suggest that heritable variation in phagocytic capacity arises via a quantitative trait architecture with variation in genes affecting the activation and/or differentiation of phagocytic cells, suggesting them as potential candidate genes underlying these phenotypic differences. © 2021 by the authors.}, keywords = {PHAGOCYTOSIS; innate immunity; FUNCTIONAL GENOMICS; Eco-immunology}, year = {2021}, eissn = {2073-4425} } @article{MTMT:32006156, title = {Macrophages and Their Organ Locations Shape Each Other in Development and Homeostasis – A Drosophila Perspective}, url = {https://m2.mtmt.hu/api/publication/32006156}, author = {Mase, A. and Augsburger, J. and Brückner, K.}, doi = {10.3389/fcell.2021.630272}, journal-iso = {FRONT CELL DEV BIOL}, journal = {FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY}, volume = {9}, unique-id = {32006156}, issn = {2296-634X}, abstract = {Across the animal kingdom, macrophages are known for their functions in innate immunity, but they also play key roles in development and homeostasis. Recent insights from single cell profiling and other approaches in the invertebrate model organism Drosophila melanogaster reveal substantial diversity among Drosophila macrophages (plasmatocytes). Together with vertebrate studies that show genuine expression signatures of macrophages based on their organ microenvironments, it is expected that Drosophila macrophage functional diversity is shaped by their anatomical locations and systemic conditions. In vivo evidence for diverse macrophage functions has already been well established by Drosophila genetics: Drosophila macrophages play key roles in various aspects of development and organogenesis, including embryogenesis and development of the nervous, digestive, and reproductive systems. Macrophages further maintain homeostasis in various organ systems and promote regeneration following organ damage and injury. The interdependence and interplay of tissues and their local macrophage populations in Drosophila have implications for understanding principles of organ development and homeostasis in a wide range of species. © Copyright © 2021 Mase, Augsburger and Brückner.}, keywords = {regeneration; MACROPHAGE; Development; Drosophila melanogaster; Homeostasis; Hemocyte; Plasmatocyte; organ microenvironment}, year = {2021}, eissn = {2296-634X} } @article{MTMT:32361805, title = {Drosophila as a Model to Study Cellular Communication Between the Hematopoietic Niche and Blood Progenitors Under Homeostatic Conditions and in Response to an Immune Stress}, url = {https://m2.mtmt.hu/api/publication/32361805}, author = {Morin-Poulard, Ismael and Tian, Yushun and Vanzo, Nathalie and Crozatier, Michele}, doi = {10.3389/fimmu.2021.719349}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {12}, unique-id = {32361805}, issn = {1664-3224}, abstract = {In adult mammals, blood cells are formed from hematopoietic stem progenitor cells, which are controlled by a complex cellular microenvironment called "niche". Drosophila melanogaster is a powerful model organism to decipher the mechanisms controlling hematopoiesis, due both to its limited number of blood cell lineages and to the conservation of genes and signaling pathways throughout bilaterian evolution. Insect blood cells or hemocytes are similar to the mammalian myeloid lineage that ensures innate immunity functions. Like in vertebrates, two waves of hematopoiesis occur in Drosophila. The first wave takes place during embryogenesis. The second wave occurs at larval stages, where two distinct hematopoietic sites are identified: subcuticular hematopoietic pockets and a specialized hematopoietic organ called the lymph gland. In both sites, hematopoiesis is regulated by distinct niches. In hematopoietic pockets, sensory neurons of the peripheral nervous system provide a microenvironment that promotes embryonic hemocyte expansion and differentiation. In the lymph gland blood cells are produced from hematopoietic progenitors. A small cluster of cells called Posterior Signaling Centre (PSC) and the vascular system, along which the lymph gland develops, act collectively as a niche, under homeostatic conditions, to control the balance between maintenance and differentiation of lymph gland progenitors. In response to an immune stress such as wasp parasitism, lymph gland hematopoiesis is drastically modified and shifts towards emergency hematopoiesis, leading to increased progenitor proliferation and their differentiation into lamellocyte, a specific blood cell type which will neutralize the parasite. The PSC is essential to control this emergency response. In this review, we summarize Drosophila cellular and molecular mechanisms involved in the communication between the niche and hematopoietic progenitors, both under homeostatic and stress conditions. Finally, we discuss similarities between mechanisms by which niches regulate hematopoietic stem/progenitor cells in Drosophila and mammals.}, keywords = {DROSOPHILA; niche; Hematopoiesis; lymph gland; immune stress}, year = {2021}, eissn = {1664-3224} } @article{MTMT:32876736, title = {Extracellular matrix protein N-glycosylation mediates immune self-tolerance in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/32876736}, author = {Mortimer, N.T. and Fischer, M.L. and Waring, A.L. and Pooja, K.R. and Kacsoh, B.Z. and Brantley, S.E. and Keebaugh, E.S. and Hill, J. and Lark, C. and Martin, J. and Bains, P. and Lee, J. and Vrailas-Mortimer, A.D. and Schlenke, T.A.}, doi = {10.1073/pnas.2017460118}, journal-iso = {P NATL ACAD SCI USA}, journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, volume = {118}, unique-id = {32876736}, issn = {0027-8424}, abstract = {In order to respond to infection, hosts must distinguish pathogens from their own tissues. This allows for the precise targeting of immune responses against pathogens and also ensures self-tolerance, the ability of the host to protect self tissues from immune damage. One way to maintain self-tolerance is to evolve a self signal and suppress any immune response directed at tissues that carry this signal. Here, we characterize the Drosophila tuSz1 mutant strain, which mounts an aberrant immune response against its own fat body. We demonstrate that this autoimmunity is the result of two mutations: 1) a mutation in the GCS1 gene that disrupts N-glycosylation of extracellular matrix proteins covering the fat body, and 2) a mutation in the Drosophila Janus Kinase ortholog that causes precocious activation of hemocytes. Our data indicate that N-glycans attached to extracellular matrix proteins serve as a self signal and that activated hemocytes attack tissues lacking this signal. The simplicity of this invertebrate self-recognition system and the ubiquity of its constituent parts suggests it may have functional homologs across animals. © 2021 National Academy of Sciences. All rights reserved.}, keywords = {Animals; Adult; Female; Male; GENE; MUTATION; MUTATION; metabolism; GENETICS; ARTICLE; HEMOCYTES; immunology; animal; growth, development and aging; innate immunity; gene mutation; controlled study; nonhuman; Drosophila melanogaster; Drosophila melanogaster; immunological tolerance; immunological tolerance; cell activation; immune response; blood cell; glycosylation; glycosylation; Autoimmunity; Autoimmunity; Extracellular Matrix Proteins; Immune Tolerance; scleroprotein; scleroprotein; Janus kinase; Janus kinase; Janus Kinases; protein glycosylation; Self Tolerance; Drosophila Proteins; Drosophila protein; FAT PAD; SELF-TOLERANCE; self-recognition; protein N-glycosylation; GCS1 gene}, year = {2021}, eissn = {1091-6490} } @article{MTMT:31868380, title = {Drosophila Hox genes induce melanized pseudo-tumors when misexpressed in hemocytes}, url = {https://m2.mtmt.hu/api/publication/31868380}, author = {Ponrathnam, T. and Saini, R. and Banu, S. and Mishra, R.K.}, doi = {10.1038/s41598-021-81472-5}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {11}, unique-id = {31868380}, issn = {2045-2322}, abstract = {Hox genes are early determinants of cell identity along the anterior–posterior body axis across bilaterians. Several late non-homeotic functions of Hox genes have emerged in a variety of processes involved in organogenesis in several organisms, including mammals. Several studies have reported the misexpression of Hox genes in a variety of malignancies including acute myeloid leukemia. The Hox genes Dfd, Ubx, abd-A and Abd-B were overexpressed via the UAS-Gal4 system using Cg-Gal4, Lsp2-Gal4, He-Gal4 and HmlD3-Gal4 as specific drivers. Genetic interaction was tested by bringing overexpression lines in heterozygous mutant backgrounds of Polycomb and trithorax group factors. Larvae were visually scored for melanized bodies. Circulating hemocytes were quantified and tested for differentiation. Pupal lethality was assessed. Expression of Dfd, Ubx and abd-A, but not Abd-B in the hematopoietic compartment of Drosophila led to the appearance of circulating melanized bodies, an increase in cell number, cell-autonomous proliferation, and differentiation of hemocytes. Pupal lethality and melanized pseudo-tumors were suppressed in Psc1 and esc2 backgrounds while polycomb group member mutations Pc1 and Su(z)123 and trithorax group member mutation TrlR85 enhanced the phenotype. Dfd, Ubx and abd-A are leukemogenic. Mutations in Polycomb and trithorax group members modulate the leukemogenic phenotype. Our RNAseq of Cg-Gal4 > UAS-abd-A hemocytes may contain genes important to Hox gene induced leukemias. © 2021, The Author(s).}, year = {2021}, eissn = {2045-2322} } @article{MTMT:32317577, title = {A parasitoid wasp of Drosophila employs preemptive and reactive strategies to deplete its host's blood cells}, url = {https://m2.mtmt.hu/api/publication/32317577}, author = {Ramroop, Johnny R. and Heavner, Mary Ellen and Razzak, Zubaidul H. and Govind, Shubha}, doi = {10.1371/journal.ppat.1009615}, journal-iso = {PLOS PATHOG}, journal = {PLOS PATHOGENS}, volume = {17}, unique-id = {32317577}, issn = {1553-7366}, abstract = {The wasps Leptopilina heterotoma parasitize and ingest their Drosophila hosts. They produce extracellular vesicles (EVs) in the venom that are packed with proteins, some of which perform immune suppressive functions. EV interactions with blood cells of host larvae are linked to hematopoietic depletion, immune suppression, and parasite success. But how EVs disperse within the host, enter and kill hematopoietic cells are not well understood. Using an antibody marker for L. heterotoma EVs, we show that these parasite-derived structures are readily distributed within the hosts' hemolymphatic system. EVs converge around the tightly clustered cells of the posterior signaling center (PSC) of the larval lymph gland, a small hematopoietic organ in Drosophila. The PSC serves as a source of developmental signals in naive animals. In wasp-infected animals, the PSC directs the differentiation of lymph gland progenitors into lamellocytes. These lamellocytes are needed to encapsulate the wasp egg and block parasite development. We found that L. heterotoma infection disassembles the PSC and PSC cells disperse into the disintegrating lymph gland lobes. Genetically manipulated PSC-less lymph glands remain non-responsive and largely intact in the face of L. heterotoma infection. We also show that the larval lymph gland progenitors use the endocytic machinery to internalize EVs. Once inside, L. heterotoma EVs damage the Rab7- and LAMP-positive late endocytic and phagolysosomal compartments. Rab5 maintains hematopoietic and immune quiescence as Rab5 knockdown results in hematopoietic over-proliferation and ectopic lamellocyte differentiation. Thus, both aspects of anti-parasite immunity, i.e., (a) phagocytosis of the wasp's immune-suppressive EVs, and (b) progenitor differentiation for wasp egg encapsulation reside in the lymph gland. These results help explain why the lymph gland is specifically and precisely targeted for destruction. The parasite's simultaneous and multipronged approach to block cellular immunity not only eliminates blood cells, but also tactically blocks the genetic programming needed for supplementary hematopoietic differentiation necessary for host success. In addition to its known functions in hematopoiesis, our results highlight a previously unrecognized phagocytic role of the lymph gland in cellular immunity. EV-mediated virulence strategies described for L. heterotoma are likely to be shared by other parasitoid wasps; their understanding can improve the design and development of novel therapeutics and biopesticides as well as help protect biodiversity.Author summary Parasitoid wasps serve as biological control agents of agricultural insect pests and are worthy of study. Many parasitic wasps develop inside their hosts to emerge as free-living adults. To overcome the resistance of their hosts, parasitic wasps use varied and ingenious strategies such as mimicry, evasion, bioactive venom, virus-like particles, viruses, and extracellular vesicles (EVs). We describe the effects of a unique class of EVs containing virulence proteins and produced in the venom of wasps that parasitize fruit flies of Drosophila species. EVs from Leptopilina heterotoma are widely distributed throughout the Drosophila hosts' circulatory system after infection. They enter and kill macrophages by destroying the very same subcellular machinery that facilitates their uptake. An important protein in this process, Rab5, is needed to maintain the identity of the macrophage; when Rab5 function is reduced, macrophages turn into a different cell type called lamellocytes. Activities in the EVs can eliminate lamellocytes as well. EVs also interfere with the hosts' genetic program that promotes lamellocyte differentiation needed to block parasite development. Thus, wasps combine specific preemptive and reactive strategies to deplete their hosts of the very cells that would otherwise sequester and kill them. These findings have applied value in agricultural pest control and medical therapeutics.}, year = {2021}, eissn = {1553-7374} } @article{MTMT:32023128, title = {Regression plane concept for analysing continuous cellular processes with machine learning}, url = {https://m2.mtmt.hu/api/publication/32023128}, author = {Szkalisity, Ábel and Piccinini, Filippo and Beleon, Attila and Balassa, Tamás and Varga, Gergely István and Migh, Ede and Molnár, Csaba and Paavolainen, Lassi and Timonen, Sanna and Banerjee, Indranil and Ikonen, Elina and Yamauchi, Yohei and Andó, István and Peltonen, Jaakko and Pietiäinen, Vilja and Honti, Viktor and Horváth, Péter}, doi = {10.1038/s41467-021-22866-x}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {12}, unique-id = {32023128}, issn = {2041-1723}, year = {2021}, eissn = {2041-1723}, orcid-numbers = {Piccinini, Filippo/0000-0002-0371-7782; Varga, Gergely István/0000-0001-9073-5788; Molnár, Csaba/0000-0002-6124-1209; Ikonen, Elina/0000-0001-8382-1135; Yamauchi, Yohei/0000-0002-8233-9133; Andó, István/0000-0002-4648-9396; Pietiäinen, Vilja/0000-0003-3125-2406} } @article{MTMT:31868552, title = {Immune cell production is targeted by parasitoid wasp virulence in a drosophila–parasitoid wasp interaction}, url = {https://m2.mtmt.hu/api/publication/31868552}, author = {Trainor, J.E. and Pooja, K.R. and Mortimer, N.T.}, doi = {10.3390/pathogens10010049}, journal-iso = {PATHOGENS}, journal = {PATHOGENS}, volume = {10}, unique-id = {31868552}, abstract = {The interactions between Drosophila melanogaster and the parasitoid wasps that infect Drosophila species provide an important model for understanding host–parasite relationships. Following parasitoid infection, D. melanogaster larvae mount a response in which immune cells (hemocytes) form a capsule around the wasp egg, which then melanizes, leading to death of the parasitoid. Previous studies have found that host hemocyte load; the number of hemocytes available for the encapsulation response; and the production of lamellocytes, an infection induced hemocyte type, are major determinants of host resistance. Parasitoids have evolved various virulence mechanisms to overcome the immune response of the D. melanogaster host, including both active immune suppression by venom proteins and passive immune evasive mechanisms. We identified a previously undescribed parasitoid species, Asobara sp. AsDen, which utilizes an active virulence mechanism to infect D. melanogaster hosts. Asobara sp. AsDen infection inhibits host hemocyte expression of msn, a member of the JNK signaling pathway, which plays a role in lamellocyte production. Asobara sp. AsDen infection restricts the production of lamellocytes as assayed by hemocyte cell morphology and altered msn expression. Our findings suggest that Asobara sp. AsDen infection alters host signaling to suppress immunity. © 2021 by the authors. Li-censee MDPI, Basel, Switzerland.}, keywords = {Female; ARTICLE; VENOM; signal transduction; PHYLOGENY; DROSOPHILA; DROSOPHILA; controlled study; nonhuman; sequence analysis; Drosophila melanogaster; immunocompetent cell; encapsulation; immune response; blood cell; principal component analysis; cell structure; immunosuppressive treatment; bacterial virulence; passive immunization; DNA extraction; Lamellocyte; Parasitoid; Sanger sequencing; Parasitoid wasp; Immune cell; Virulence strategy; hemolymphatic system}, year = {2021}, eissn = {2076-0817}, pages = {1-16} } @article{MTMT:32358968, title = {Proteomics of purified lamellocytes from Drosophila melanogaster HopTum-l identifies new membrane proteins and networks involved in their functions}, url = {https://m2.mtmt.hu/api/publication/32358968}, author = {Wan, Bin and Belghazi, Maya and Lemauf, Severine and Poirie, Marylene and Gatti, Jean-Luc}, doi = {10.1016/j.ibmb.2021.103584}, journal-iso = {INSECT BIOCHEM MOLEC}, journal = {INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY}, volume = {134}, unique-id = {32358968}, issn = {0965-1748}, abstract = {In healthy Drosophila melanogaster larvae, plasmatocytes and crystal cells account for 95% and 5% of the hemocytes, respectively. A third type of hemocytes, lamellocytes, are rare, but their number increases after oviposition by parasitoid wasps. The lamellocytes form successive layers around the parasitoid egg, leading to its encapsulation and melanization, and finally the death of this intruder. However, the total number of lamellocytes per larva remains quite low even after parasitoid infestation, making direct biochemical studies difficult. Here, we used the HopTum-l mutant strain that constitutively produces large numbers of lamellocytes to set up a purification method and analyzed their major proteins by 2D gel electrophoresis and their plasma membrane surface proteins by 1D SDS-PAGE after affinity purification. Mass spectrometry identified 430 proteins from 2D spots and 344 affinity-purified proteins from 1D bands, for a total of 639 unique proteins. Known lamellocyte markers such as PPO3 and the myospheroid integrin were among the components identified with specific chaperone proteins. Affinity purification detected other integrins, as well as a wide range of integrin-associated proteins involved in the formation and function of cell-cell junctions. Overall, the newly identified proteins indicate that these cells are highly adapted to the encapsulation process (recognition, motility, adhesion, signaling), but may also have several other physiological functions (such as secretion and internalization of vesicles) under different signaling pathways. These results provide the basis for further in vivo and in vitro studies of lamellocytes, including the development of new markers to identify coexisting populations and their respective origins and functions in Drosophila immunity.}, keywords = {Drosophila melanogaster; protein purification; proteomics; lamellocytes; Hemocytes purification; Q-orbitrap spectrometry}, year = {2021}, eissn = {1879-0240}, orcid-numbers = {Belghazi, Maya/0000-0002-3600-4754} } @article{MTMT:31596046, title = {Cellular and humoral immune interactions between Drosophila and its parasitoids}, url = {https://m2.mtmt.hu/api/publication/31596046}, author = {Yang, L. and Qiu, L.-M. and Fang, Q. and Stanley, D.W. and Ye, G.-Y.}, doi = {10.1111/1744-7917.12863}, journal-iso = {INSECT SCI}, journal = {INSECT SCIENCE}, volume = {28}, unique-id = {31596046}, issn = {1672-9609}, abstract = {The immune interactions occurring between parasitoids and their host insects, especially in Drosophila–wasp models, have long been the research focus of insect immunology and parasitology. Parasitoid infestation in Drosophila is counteracted by its multiple natural immune defense systems, which include cellular and humoral immunity. Occurring in the hemocoel, cellular immune responses involve the proliferation, differentiation, migration and spreading of host hemocytes and parasitoid encapsulation by them. Contrastingly, humoral immune responses rely more heavily on melanization and on the Toll, Imd and Jak/Stat immune pathways associated with antimicrobial peptides along with stress factors. On the wasps’ side, successful development is achieved by introducing various virulence factors to counteract immune responses of Drosophila. Some or all of these factors manipulate the host's immunity for successful parasitism. Here we review current knowledge of the cellular and humoral immune interactions between Drosophila and its parasitoids, focusing on the defense mechanisms used by Drosophila and the strategies evolved by parasitic wasps to outwit it. © 2020 Institute of Zoology, Chinese Academy of Sciences}, keywords = {VENOM; DROSOPHILA; Immunity; Parasitoid; VIRUS-LIKE PARTICLES}, year = {2021}, eissn = {1744-7917}, pages = {1208-1227} } @article{MTMT:32424572, title = {Comparative transcriptome analysis reveals a potential mechanism for host nutritional manipulation after parasitization by Leptopilina boulardi}, url = {https://m2.mtmt.hu/api/publication/32424572}, author = {Zhou, Sicong and Lu, Yueqi and Wang, Ying and Chen, Jiani and Pang, Lan and Zhang, Qichao and Sheng, Yifeng and Liu, Zhiguo and Shi, Min and Chen, Xuexin and Huang, Jianhua}, doi = {10.1016/j.cbd.2021.100862}, journal-iso = {COMP BIOCHEM PHYS D}, journal = {COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY D-GENOMICS & PROTEOMICS}, volume = {39}, unique-id = {32424572}, issn = {1744-117X}, abstract = {Parasitoids have been extensively found to manipulate nutrient amounts of their hosts to benefit their own development and survival, but the underlying mechanisms are largely unknown. Leptopilina boulardi (Hymenoptera: Figitidae) is a larval-pupal endoparasitoid wasp of Drosophila melanogaster whose survival relies on the nutrients provided by its Drosophila host. Here, we used RNA-seq to compare the gene expression levels of the host midgut at 24 h and 48 h post L. boulardi parasitization. We obtained 95 and 191 differentially expressed genes (DEGs) in the parasitized host midgut at 24 h and 48 h post L. boulardi parasitization, respectively. A KEGG analysis revealed that several metabolic pathways were significantly enriched in the upregulated DEGs, and these pathways included "starch and sucrose metabolism" and "galactose metabolism". A functional annotation analysis showed that four classes of genes involved in carbohydrate digestion process had increased expression levels in the midgut post L. boulardi parasitization than nonparasitized groups: glucosidase, mannosidase, chitinase and amylase. Genes involved in protein digestion process were also found among the DEGs, and most of these genes, which belonged to the metallopeptidase and serine-type endopeptidase families, were found at higher expression levels in the parasitized host midgut comparing with nonparasitized hosts. Moreover, some immune genes, particularly those involved in the Toll and Imd pathways, also exhibited high expression levels after L. boulardi parasitization. Our study provides large-scale transcriptome data and identifies sets of DEGs between parasitized and nonparasitized host midgut tissues at 24 h and 48 h post L. boulardi parasitization. These resources help improve our understanding of how parasitoid infection affects the nutrient components in the hosts.}, keywords = {DIFFERENTIALLY EXPRESSED GENES; Transcriptome; Parasitoid; Host midgut; Nutritional manipulation}, year = {2021}, eissn = {1878-0407} } @article{MTMT:31468836, title = {Maternal Priming of Offspring Immune System in Drosophila}, url = {https://m2.mtmt.hu/api/publication/31468836}, author = {Bozler, Julianna and Kacsoh, Balint Z. and Bosco, Giovanni}, doi = {10.1534/g3.119.400852}, journal-iso = {G3-GENES GENOM GENET}, journal = {G3-GENES GENOMES GENETICS}, volume = {10}, unique-id = {31468836}, issn = {2160-1836}, abstract = {Immune priming occurs when a past infection experience leads to a more effective immune response upon a secondary exposure to the infection or pathogen. In some instances, parents are able to transmit immune priming to their offspring, creating a subsequent generation with a superior immune capability, through processes that are not yet fully understood. Using a parasitoid wasp, which infects larval stages of Drosophila melanogaster, we describe an example of an intergenerational inheritance of immune priming. This phenomenon is anticipatory in nature and does not rely on parental infection, but rather, when adult fruit flies are cohabitated with a parasitic wasp, they produce offspring that are more capable of mounting a successful immune response against a parasitic macro-infection. This increase in offspring survival correlates with a more rapid induction of lamellocytes, a specialized immune cell. RNA-sequencing of the female germline identifies several differentially expressed genes following wasp exposure, including the peptiodoglycan recognition protein-LB (PGRP-LB). We find that genetic manipulation of maternal PGRP-LB identifies this gene as a key element in this intergenerational phenotype.}, keywords = {Immunity; immune priming; intergenerational; transgenerational; leptopilina heterotoma; leptopilina victoriae; PGRP-LB}, year = {2020}, eissn = {2160-1836}, pages = {165-175}, orcid-numbers = {Bosco, Giovanni/0000-0002-8889-9895} } @article{MTMT:31460653, title = {Temporal specificity and heterogeneity ofDrosophilaimmune cells}, url = {https://m2.mtmt.hu/api/publication/31460653}, author = {Cattenoz, Pierre B. and Sakr, Rosy and Pavlidaki, Alexia and Delaporte, Claude and Riba, Andrea and Molina, Nacho and Hariharan, Nivedita and Mukherjee, Tina and Giangrande, Angela}, doi = {10.15252/embj.2020104486}, journal-iso = {EMBO J}, journal = {EMBO JOURNAL}, volume = {39}, unique-id = {31460653}, issn = {0261-4189}, abstract = {Immune cells provide defense against non-self and have recently been shown to also play key roles in diverse processes such as development, metabolism, and tumor progression. The heterogeneity ofDrosophilaimmune cells (hemocytes) remains an open question. Using bulk RNA sequencing, we find that the hemocytes display distinct features in the embryo, a closed and rapidly developing system, compared to the larva, which is exposed to environmental and metabolic challenges. Through single-cell RNA sequencing, we identify fourteen hemocyte clusters present in unchallenged larvae and associated with distinct processes, e.g., proliferation, phagocytosis, metabolic homeostasis, and humoral response. Finally, we characterize the changes occurring in the hemocyte clusters upon wasp infestation, which triggers the differentiation of a novel hemocyte type, the lamellocyte. This first molecular atlas of hemocytes provides insights and paves the way to study the biology of theDrosophilaimmune cells in physiological and pathological conditions.}, keywords = {Drosophila melanogaster; immune cells; Single-cell RNA-seq; wasp infestation}, year = {2020}, eissn = {1460-2075} } @article{MTMT:31868487, title = {Single-cell transcriptome maps of myeloid blood cell lineages in Drosophila}, url = {https://m2.mtmt.hu/api/publication/31868487}, author = {Cho, B. and Yoon, S.-H. and Lee, D. and Koranteng, F. and Tattikota, S.G. and Cha, N. and Shin, M. and Do, H. and Hu, Y. and Oh, S.Y. and Lee, D. and Vipin, Menon A. and Moon, S.J. and Perrimon, N. and Nam, J.-W. and Shim, J.}, doi = {10.1038/s41467-020-18135-y}, journal-iso = {NAT COMMUN}, journal = {NATURE COMMUNICATIONS}, volume = {11}, unique-id = {31868487}, issn = {2041-1723}, abstract = {The Drosophila lymph gland, the larval hematopoietic organ comprised of prohemocytes and mature hemocytes, has been a valuable model for understanding mechanisms underlying hematopoiesis and immunity. Three types of mature hemocytes have been characterized in the lymph gland: plasmatocytes, lamellocytes, and crystal cells, which are analogous to vertebrate myeloid cells, yet molecular underpinnings of the lymph gland hemocytes have been less investigated. Here, we use single-cell RNA sequencing to comprehensively analyze heterogeneity of developing hemocytes in the lymph gland, and discover previously undescribed hemocyte types including adipohemocytes, stem-like prohemocytes, and intermediate prohemocytes. Additionally, we identify the developmental trajectory of hemocytes during normal development as well as the emergence of the lamellocyte lineage following active cellular immunity caused by wasp infestation. Finally, we establish similarities and differences between embryonically derived- and larval lymph gland hemocytes. Altogether, our study provides detailed insights into the hemocyte development and cellular immune responses at single-cell resolution. © 2020, The Author(s).}, keywords = {Animals; metabolism; BLOOD; GENETICS; ARTICLE; RNA; DROSOPHILA; HEMOCYTES; animal; MAP; Cell Differentiation; Cell Differentiation; physiology; Cytology; nonhuman; Host-Parasite Interactions; Immunity; host parasite interaction; pathogenicity; pathology; parasitology; Vertebrata; immune system; Animals, Genetically Modified; Drosophila melanogaster; Drosophila melanogaster; Gene Expression Profiling; Gene Expression Profiling; cellular immunity; immune response; immune response; blood cell; blood cell; transcriptomics; lymphoid tissue; lymphoid tissue; transgenic animal; Cell Lineage; Cell Lineage; Transcriptome; Transcriptome; Transcriptome; lymph node; Hematopoiesis; Hematopoiesis; detection method; Wasps; myeloid progenitor cell; WASP; WASP; Single-Cell Analysis; single cell analysis; RNA-Seq; cells by body anatomy; cell component; single cell RNA seq; Ectoparasitosis; Ectoparasitic Infestations}, year = {2020}, eissn = {2041-1723} } @article{MTMT:30819399, title = {Cellular Immune Response Involving Multinucleated Giant Hemocytes with Two-Step Genome Amplification in the Drosophilid Zaprionus indianus}, url = {https://m2.mtmt.hu/api/publication/30819399}, author = {Cinege, Gyöngyi Ilona and Lerner, Zita and Magyar, Lilla Brigitta and Soós, Bálint and Tóth, Renáta and Kristó, Ildikó and Vilmos, Péter and Juhász, Gábor and Kovács, Attila Lajos and Hegedűs, Zoltán and Sensen, Christoph W. and Kurucz, Judit Éva and Andó, István}, doi = {10.1159/000502646}, journal-iso = {J INNATE IMMUN}, journal = {JOURNAL OF INNATE IMMUNITY}, volume = {12}, unique-id = {30819399}, issn = {1662-811X}, year = {2020}, eissn = {1662-8128}, pages = {257-272}, orcid-numbers = {Juhász, Gábor/0000-0001-8548-8874; Andó, István/0000-0002-4648-9396} } @article{MTMT:31470099, title = {Drosophilamelanogaster Responses against Entomopathogenic Nematodes: Focus on Hemolymph Clots}, url = {https://m2.mtmt.hu/api/publication/31470099}, author = {Dziedziech, Alexis and Shivankar, Sai and Theopold, Ulrich}, doi = {10.3390/insects11010062}, journal-iso = {INSECTS}, journal = {INSECTS}, volume = {11}, unique-id = {31470099}, abstract = {Several insect innate immune mechanisms are activated in response to infection by entomopathogenic nematodes (EPNs). In this review, we focus on the coagulation of hemolymph, which acts to stop bleeding after injury and prevent access of pathogens to the body cavity. After providing a general overview of invertebrate coagulation systems, we discuss recent findings in Drosophila melanogaster which demonstrate that clots protect against EPN infections. Detailed analysis at the cellular level provided insight into the kinetics of the secretion of Drosophila coagulation factors, including non-classical modes of secretion. Roughly, clot formation can be divided into a primary phase in which crosslinking of clot components depends on the activity of Drosophila transglutaminase and a secondary, phenoloxidase (PO)-dependent phase, characterized by further hardening and melanization of the clot matrix. These two phases appear to play distinct roles in two commonly used EPN infection models, namely Heterorhabditis bacteriophora and Steinernema carpocapsae. Finally, we discuss the implications of the coevolution between parasites such as EPNs and their hosts for the dynamics of coagulation factor evolution.}, keywords = {TRANSGLUTAMINASE; COAGULATION; SECRETION; HEMOCYTES; innate immunity; Nematodes; clotting; phenoloxidase; insect immunity}, year = {2020}, eissn = {2075-4450}, orcid-numbers = {Dziedziech, Alexis/0000-0001-7647-7639; Theopold, Ulrich/0000-0002-1009-8254} } @article{MTMT:31469242, title = {Single-cell RNA sequencing identifies novel cell types in Drosophila blood}, url = {https://m2.mtmt.hu/api/publication/31469242}, author = {Fu, Yulong and Huang, Xiaohu and Zhang, Peng and van de Leemput, Joyce and Han, Zhe}, doi = {10.1016/j.jgg.2020.02.004}, journal-iso = {J GENET GENOMICS}, journal = {JOURNAL OF GENETICS AND GENOMICS}, volume = {47}, unique-id = {31469242}, issn = {1673-8527}, abstract = {Drosophila has been extensively used to model the human blood-immune system, as both systems share many developmental and immune response mechanisms. However, while many human blood cell types have been identified, only three were found in flies: plasmatocytes, crystal cells and lamellocytes. To better understand the complexity of fly blood system, we used single-cell RNA sequencing technology to generate comprehensive gene expression profiles for Drosophila circulating blood cells. In addition to the known cell types, we identified two new Drosophila blood cell types: thanacytes and primocytes. Thanacytes, which express many stimulus response genes, are involved in distinct responses to different types of bacteria. Primocytes, which express cell fate commitment and signaling genes, appear to be involved in keeping stem cells in the circulating blood. Furthermore, our data revealed four novel plasmatocyte subtypes (Ppn(+), CAH7(+), Lsp(+) and reservoir plasmatocytes), each with unique molecular identities and distinct predicted functions. We also identified cross-species markers from Drosophila hemocytes to human blood cells. Our analysis unveiled a more complex Drosophila blood system and broadened the scope of using Drosophila to model human blood system in development and disease. Copyright (C) 2020, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, and Genetics Society of China. Published by Elsevier Limited and Science Press. All rights reserved.}, keywords = {BLOOD; DROSOPHILA; Plasmatocyte; Single-cell RNA-seq; Thanacyte; Primocyte}, year = {2020}, eissn = {1873-5533}, pages = {175-186}, orcid-numbers = {Zhang, Peng/0000-0002-6218-1885; Han, Zhe/0000-0002-5177-7798} } @article{MTMT:31468406, title = {Speculations on the evolution of humoral adaptive immunity}, url = {https://m2.mtmt.hu/api/publication/31468406}, author = {Horton, Miles B. and Hawkins, Edwin D. and Heinzel, Susanne and Hodgkin, Philip D.}, doi = {10.1111/imcb.12323}, journal-iso = {IMMUNOL CELL BIOL}, journal = {IMMUNOLOGY AND CELL BIOLOGY}, volume = {98}, unique-id = {31468406}, issn = {0818-9641}, abstract = {The protection of a multicellular organism from infection, at both cell and humoral levels, has been a tremendous driver of gene selection and cellular response strategies. Here we focus on a critical event in the development of humoral immunity: The transition from principally innate responses to a system of adaptive cell selection, with all the attendant mechanical problems that must be solved in order for it to work effectively. Here we review recent advances, but our major goal is to highlight that the development of adaptive immunity resulted from the adoption, reuse and repurposing of an ancient, autonomous cellular program that combines and exploits three titratable cellular fate timers. We illustrate how this common cell machinery recurs and appears throughout biology, and has been essential for the evolution of complex organisms, at many levels of scale.}, keywords = {PROLIFERATION; humoral immunity; B cells; cell signaling; cell fate; Comparative immunology; evolutionary immunology}, year = {2020}, eissn = {1440-1711}, pages = {439-448} } @article{MTMT:31686512, title = {Development of two continuous hemocyte cell sublines in the Asian corn borerOstrinia furnacalisand the identification of molecular markers for hemocytes}, url = {https://m2.mtmt.hu/api/publication/31686512}, author = {Hu, Jian and Du, Yan and Meng, Meng and Dong, Yipei and Peng, Jiewen}, doi = {10.1111/1744-7917.12854}, journal-iso = {INSECT SCI}, journal = {INSECT SCIENCE}, unique-id = {31686512}, issn = {1672-9609}, abstract = {Granulocytes and plasmatocytes play important roles in clearing foreign objects in insects, but it is difficult to distinguish between them in immune reactions. Based on the hemocyte cell line SYSU-OfHe-C established at our lab, two cell sublines, SYSU-OfHe-C Granulocyte (Gr cells) and SYSU-OfHe-C Plasmatocyte (Pl cells), which possess the morphological characteristics of granulocytes and plasmatocytes, respectively, were established. Gr and Pl cells showed different behaviors in immune reactions, such as spreading, phagocytosis and encapsulation. Pl cells were easier to spread, but Gr cells tended to undergo aggregation, indicating that they may take different strategies to clear foreign objects. These results also suggested that granulocytes and plasmatocytes may express some different proteins. By comparing the gene expression in cells from the two sublines, 1662 differentially expressed genes were identified, and 13 out of 30 transmembrane proteins highly expressed in Pl cells (six) or Gr cells (seven) were further screened and confirmed by reverse-transcription polymerase chain reaction (PCR). Finally, three transmembrane genes specifically expressed in Pl cells and two transmembrane genes specifically expressed in Gr cells were screened out based on their expressions in immune reactions by quantitative PCR analysis. These genes may potentially be used as molecular markers to distinguish between granulocytes and plasmatocytes inOstrinia furnacalis, and further to clarify the functions of immune hemocytes in cellular immune reaction such as encapsulation and so on.}, keywords = {INSECT; Molecular marker; granulocyte; Hemocyte; Plasmatocyte; cell sublines}, year = {2020}, eissn = {1744-7917} } @article{MTMT:31686813, title = {Regulation ofDrosophilaHematopoiesis in Lymph Gland: From a Developmental Signaling Point of View}, url = {https://m2.mtmt.hu/api/publication/31686813}, author = {Lan, Wenwen and Liu, Sumin and Zhao, Long and Su, Ying}, doi = {10.3390/ijms21155246}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {21}, unique-id = {31686813}, issn = {1661-6596}, abstract = {TheDrosophilahematopoietic system is becoming increasingly attractive for its simple blood cell lineage and its developmental and functional parallels with the vertebrate system. As the dedicated organ forDrosophilalarval hematopoiesis, the lymph gland harbors both multipotent stem-like progenitor cells and differentiated blood cells. The balance between progenitor maintenance and differentiation in the lymph gland must be precisely and tightly controlled. Multiple developmental signaling pathways, such as Notch, Hedgehog, and Wnt/Wingless, have been demonstrated to regulate the hematopoietic processes in the lymph gland. Focusing on blood cell maintenance and differentiation, this article summarizes the functions of several classic developmental signaling pathways for lymph gland growth and patterning, highlighting the important roles of developmental signaling during lymph gland development as well asDrosophilalarval hematopoiesis.}, keywords = {Drosophila melanogaster; Hematopoiesis; lymph gland; developmental signaling}, year = {2020}, eissn = {1422-0067}, orcid-numbers = {Su, Ying/0000-0002-8466-0043} } @article{MTMT:31868549, title = {Metabolic control of cellular immune-competency by odors in drosophila}, url = {https://m2.mtmt.hu/api/publication/31868549}, author = {Madhwal, S. and Shin, M. and Kapoor, A. and Goyal, M. and Joshi, M.K. and Rehman, P.M.U. and Gor, K. and Shim, J. and Mukherjee, T.}, doi = {10.7554/ELIFE.60376}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {9}, unique-id = {31868549}, issn = {2050-084X}, keywords = {metabolism; INFECTION; Immunity; olfaction; Hematopoiesis; SUCCINATE; GABA-shunt; HIFα}, year = {2020}, eissn = {2050-084X}, pages = {1-93} } @article{MTMT:31509173, title = {Discovery of aspirin-triggered eicosanoid-like mediators in a Drosophila metainflammation blood tumor model}, url = {https://m2.mtmt.hu/api/publication/31509173}, author = {Panettieri, Silvio and Paddibhatla, Indira and Chou, Jennifer and Rajwani, Roma and Moore, Rebecca S. and Goncharuk, Tamara and John, George and Govind, Shubha}, doi = {10.1242/jcs.236141}, journal-iso = {J CELL SCI}, journal = {JOURNAL OF CELL SCIENCE}, volume = {133}, unique-id = {31509173}, issn = {0021-9533}, abstract = {Epidemiologic studies have linked the use of aspirin to a decline in chronic inflammation that underlies many human diseases, including some cancers. Aspirin reduces the levels of cyclooxygenase-mediated pro-inflammatory prostaglandins, promotes the production of proresolution molecules, and triggers the production of anti-inflammatory electrophilic mono-oxygenated (EFOX) lipid mediators. We investigated the effects of aspirin in fruit fly models of chronic inflammation. Ectopic Toll/NF-kappa B and JAK/STAT signaling in mutant D. melanogaster results in overproliferation of hematopoietic blood progenitors resulting in the formation of granuloma-like tumors. Ectopic JAK-STAT signaling also leads to metabolic inflammation. We report that aspirin-treated mutant flies experience reduction in metabolic inflammation, mitosis, ectopic immune signaling, and macrophage infiltration. Moreover, these flies synthesize 13-HODE, and aspirin triggers 13-oxoODE (13-EFOX-L-2) production. Providing the precursor of 13-HODE, linoleic acid, or performing targeted knockdown of the transcription factor STAT in inflammatory blood cells, boosts 13-EFOX-L-2 levels while decreasing metabolic inflammation. Thus, hematopoietic cells regulate metabolic inflammation in flies, and their effects can be reversed by pharmaceutical or dietary intervention, suggesting deep phylogenetic conservation in the ability of animals to resolve inflammation and repair tissue damage. These findings can help identify novel treatment targets in humans.}, keywords = {RESOLUTION; MACROPHAGES; DROSOPHILA; ASPIRIN; fatty acid; SYSTEMIC INFLAMMATION; Eicosanoid; NE-kappa B; EFOX; 13-NODE; 13-oxoODE}, year = {2020}, eissn = {1477-9137}, orcid-numbers = {Paddibhatla, Indira/0000-0002-3057-2160; John, George/0000-0002-0382-1256} } @article{MTMT:31509180, title = {Ex vivo characterization of the circulating hemocytes of bed bugs and their responses to bacterial exposure}, url = {https://m2.mtmt.hu/api/publication/31509180}, author = {Potts, Rashaun and King, Jonas G. and Pietri, Jose E.}, doi = {10.1016/j.jip.2020.107422}, journal-iso = {J INVERTEBR PATHOL}, journal = {JOURNAL OF INVERTEBRATE PATHOLOGY}, volume = {174}, unique-id = {31509180}, issn = {0022-2011}, abstract = {Bed bugs (Cimex spp.) are urban pests of global importance. Knowledge of the immune system of bed bugs has implications for understanding their susceptibility to biological control agents, their potential to transmit human pathogens, and the basic comparative immunology of insects. Nonetheless, the immunological repertoire of the family Cimicidae remains poorly characterized. Here, we use microscopy, flow cytometry, and RNA sequencing to provide a basal characterization of the circulating hemocytes of the common bed bug, Cimex lectularius. We also examine the responses of these specialized cells to E. coli exposure using the same techniques. Our results show that circulating hemocytes are comprised of at least four morphologically distinct cell types that are capable of phagocytosis, undergo degranulation, and exhibit additional markers of activation following stimulation, including size shift and DNA replication. Furthermore, transcriptomic profiling reveals expression of predicted Toll/IMD signaling pathway components, antimicrobial effectors and other potentially immunoresponsive genes in these cells. Together, our data demonstrate the conservation of several canonical cellular immune responses in the common bed bug and provide a foundation for additional mechanistic immunological studies with specific pathogens of interest.}, keywords = {BACTERIA; Immunity; immune response; Hemocyte; Cimex; Bed bug}, year = {2020}, eissn = {1096-0805} } @article{MTMT:31468577, title = {Comparative RNA-Seq analyses ofDrosophilaplasmatocytes reveal gene specific signatures in response to clean injury and septic injury}, url = {https://m2.mtmt.hu/api/publication/31468577}, author = {Ramond, Elodie and Dudzic, Jan Paul and Lemaitre, Bruno}, doi = {10.1371/journal.pone.0235294}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {15}, unique-id = {31468577}, issn = {1932-6203}, abstract = {Drosophila melanogaster's blood cells (hemocytes) play essential roles in wound healing and are involved in clearing microbial infections. Here, we report the transcriptional changes of larval plasmatocytes after clean injury or infection with the Gram-negative bacteriumEscherichia colior the Gram-positive bacteriumStaphylococcus aureuscompared to hemocytes recovered from unchallenged larvae via RNA-Sequencing. This study reveals 676 differentially expressed genes (DEGs) in hemocytes from clean injury samples compared to unchallenged samples, and 235 and 184 DEGs inE.coliandS.aureussamples respectively compared to clean injury samples. The clean injury samples showed enriched DEGs for immunity, clotting, cytoskeleton, cell migration, hemocyte differentiation, and indicated a metabolic reprogramming to aerobic glycolysis, a well-defined metabolic adaptation observed in mammalian macrophages. Microbial infections trigger significant transcription of immune genes, with significant differences between theE.coliandS.aureussamples suggesting that hemocytes have the ability to engage various programs upon infection. Collectively, our data bring new insights onDrosophilahemocyte function and open the route to post-genomic functional analysis of the cellular immune response.}, year = {2020}, eissn = {1932-6203}, orcid-numbers = {Ramond, Elodie/0000-0003-4775-7070; Lemaitre, Bruno/0000-0001-7970-1667} } @article{MTMT:31469236, title = {The adipokine NimrodB5 regulates peripheral hematopoiesis in Drosophila}, url = {https://m2.mtmt.hu/api/publication/31469236}, author = {Ramond, Elodie and Petrignani, Bianca and Dudzic, Jan Paul and Boquete, Jean-Philippe and Poidevin, Mickael and Kondo, Shu and Lemaitre, Bruno}, doi = {10.1111/febs.15237}, journal-iso = {FEBS J}, journal = {FEBS JOURNAL}, unique-id = {31469236}, issn = {1742-464X}, abstract = {In animals, growth is regulated by the complex interplay between paracrine and endocrine signals. When food is scarce, tissues compete for nutrients, leading to critical resource allocation and prioritization. Little is known about how the immune system maturation is coordinated with the growth of other tissues. Here, we describe a signaling mechanism that regulates the number of hemocytes (blood cells) according to the nutritional state of the Drosophila larva. Specifically, we found that a secreted protein, NimB5, is produced in the fat body upon nutrient scarcity downstream of metabolic sensors and ecdysone signaling. NimB5 is then secreted and binds to hemocytes to down-regulate their proliferation and adhesion. Blocking this signaling loop results in conditional lethality when larvae are raised on a poor diet, due to excessive hemocyte numbers and insufficient energy storage. Similar regulatory mechanisms shaping the immune system in response to nutrient availability are likely to be widespread in animals.}, keywords = {metabolism; GROWTH; DROSOPHILA; TRADE-OFF; Nimrod; organ prioritization; peripheral hematopoiesis}, year = {2020}, eissn = {1742-4658}, orcid-numbers = {Ramond, Elodie/0000-0003-4775-7070; Lemaitre, Bruno/0000-0001-7970-1667} } @article{MTMT:31871705, title = {Drosophila as a Model System to Investigate the Effects of Mitochondrial Variation on Innate Immunity}, url = {https://m2.mtmt.hu/api/publication/31871705}, author = {Salminen, T.S. and Vale, P.F.}, doi = {10.3389/fimmu.2020.00521}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {11}, unique-id = {31871705}, issn = {1664-3224}, abstract = {Understanding why the response to infection varies between individuals remains one of the major challenges in immunology and infection biology. A substantial proportion of this heterogeneity can be explained by individual genetic differences which result in variable immune responses, and there are many examples of polymorphisms in nuclear-encoded genes that alter immunocompetence. However, how immunity is affected by genetic polymorphism in an additional genome, inherited maternally inside mitochondria (mtDNA), has been relatively understudied. Mitochondria are increasingly recognized as important mediators of innate immune responses, not only because they are the main source of energy required for costly immune responses, but also because by-products of mitochondrial metabolism, such as reactive oxygen species (ROS), may have direct microbicidal action. Yet, it is currently unclear how naturally occurring variation in mtDNA contributes to heterogeneity in infection outcomes. In this review article, we describe potential sources of variation in mitochondrial function that may arise due to mutations in vital nuclear and mitochondrial components of energy production or due to a disruption in mito-nuclear crosstalk. We then highlight how these changes in mitochondrial function can impact immune responses, focusing on their effects on ATP- and ROS-generating pathways, as well as immune signaling. Finally, we outline how being a powerful and genetically tractable model of infection, immunity and mitochondrial genetics makes the fruit fly Drosophila melanogaster ideally suited to dissect mitochondrial effects on innate immune responses to infection. © Copyright © 2020 Salminen and Vale.}, keywords = {PHENOTYPE; INFECTION; signal transduction; review; Cell Differentiation; innate immunity; innate immunity; Mitochondria; nonhuman; cell proliferation; Gene Expression; Drosophila melanogaster; Drosophila melanogaster; Genetic Variation; Gene Dosage; mtDNA; glutathione peroxidase; immune response; Reactive oxygen species; Superoxide dismutase; reactive oxygen metabolite; mitochondrion; MITOCHONDRIAL RESPIRATION; gene sequence; transcription regulation; DNA polymorphism; gene overexpression; oxidative phosphorylation; oxidative phosphorylation; toll like receptor 9; Pattern recognition receptor; Cybrid; Oxidative stress}, year = {2020}, eissn = {1664-3224} } @article{MTMT:31467726, title = {Subpopulation of Macrophage-Like Plasmatocytes Attenuates Systemic Growth via JAK/STAT in the Drosophila Fat Body}, url = {https://m2.mtmt.hu/api/publication/31467726}, author = {Shin, Mingyu and Cha, Nuri and Koranteng, Ferdinand and Cho, Bumsik and Shim, Jiwon}, doi = {10.3389/fimmu.2020.00063}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {11}, unique-id = {31467726}, issn = {1664-3224}, abstract = {Drosophila hemocytes, like those of mammals, are given rise from two distinctive phases during both the embryonic and larval hematopoiesis. Embryonically derived hemocytes, mostly composed of macrophage-like plasmatocytes, are largely identified by genetic markers. However, the cellular diversity and distinct functions of possible subpopulations within plasmatocytes have not been explored in Drosophila larvae. Here, we show that larval plasmatocytes exhibit differential expressions of Hemolectin (Hml) and Peroxidasin (Pxn) during development. Moreover, removal of plasmatocytes by overexpressing pro-apoptotic genes, hid and reaper in Hml-positive plasmatocytes, feeding high sucrose diet, or wasp infestation results in increased circulating hemocytes that are Hml-negative. Interestingly these Hml-negative plasmatocytes retain Pxn expression, and animals expressing Hml-negative and Pxn-positive subtype largely attenuate growth and abrogate metabolism. Furthermore, elevated levels of a cytokine, unpaired 3, are detected when Hml-positive hemocytes are ablated, which in turn activates JAK/STAT activity in several tissues including the fat body. Finally, we observed that insulin signaling is inhibited in this background, which can be recovered by concurrent loss of upd3. Overall, this study highlights heterogeneity in Drosophila plasmatocytes and a functional plasticity of each subtype, which reaffirms extension of their role beyond immunity into metabolic regulation for cooperatively maintaining internal homeostatic balance.}, keywords = {Drosophila melanogaster; Peroxidasin; insulin signaling; plasmatocytes; JAK/STAT; upd3; Hemolectin}, year = {2020}, eissn = {1664-3224}, orcid-numbers = {Koranteng, Ferdinand/0000-0002-0545-2423; Shim, Jiwon/0000-0003-2409-1130} } @article{MTMT:31468416, title = {A single-cell survey of Drosophila blood}, url = {https://m2.mtmt.hu/api/publication/31468416}, author = {Tattikota, Sudhir Gopal and Cho, Bumsik and Liu, Yifang and Hu, Yanhui and Barrera, Victor and Steinbaugh, Michael J. and Yoon, Sang-Ho and Comjean, Aram and Li, Fangge and Dervis, Franz and Hung, Ruei-Jiun and Nam, Jin-Wu and Sui, Shannan Ho and Shim, Jiwon and Perrimon, Norbert}, doi = {10.7554/eLife.54818}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {9}, unique-id = {31468416}, issn = {2050-084X}, abstract = {Drosophila blood cells, called hemocytes, are classified into plasmatocytes, crystal cells, and lamellocytes based on the expression of a few marker genes and cell morphologies, which are inadequate to classify the complete hemocyte repertoire. Here, we used single-cell RNA sequencing (scRNA-seq) to map hemocytes across different inflammatory conditions in larvae. We resolved plasmatocytes into different states based on the expression of genes involved in cell cycle, antimicrobial response, and metabolism together with the identification of intermediate states. Further, we discovered rare subsets within crystal cells and lamellocytes that express fibroblast growth factor (FGF) ligand branchless and receptor breathless, respectively. We demonstrate that these FGF components are required for mediating effective immune responses against parasitoid wasp eggs, highlighting a novel role for FGF signaling in inter-hemocyte crosstalk. Our scRNA-seq analysis reveals the diversity of hemocytes and provides a rich resource of gene expression profiles for a systems-level understanding of their functions.}, year = {2020}, eissn = {2050-084X}, orcid-numbers = {Tattikota, Sudhir Gopal/0000-0003-0318-5533; Cho, Bumsik/0000-0003-1989-0624; Yoon, Sang-Ho/0000-0003-2611-5554} } @article{MTMT:32601705, title = {Editorial: Recent Advances in Drosophila Cellular and Humoral Innate Immunity}, url = {https://m2.mtmt.hu/api/publication/32601705}, author = {Vesala, L. and Hultmark, D. and Valanne, S.}, doi = {10.3389/fimmu.2020.598618}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {11}, unique-id = {32601705}, issn = {1664-3224}, keywords = {Animals; Inflammation; Humans; metabolism; metabolism; PHAGOCYTOSIS; PHENOTYPE; GENETICS; EVOLUTION; BACTERIA; signal transduction; signal transduction; DROSOPHILA; DROSOPHILA; immunology; human; animal; editorial; Biomarkers; innate immunity; innate immunity; defensin; INSULIN SENSITIVITY; Nerve Degeneration; nonhuman; sex difference; biological marker; RNA Interference; Drosophila melanogaster; Drosophila melanogaster; unclassified drug; antiviral activity; humoral immunity; humoral immunity; cellular immunity; cellular immunity; immune response; blood cell; Immunity, Innate; mitochondrial DNA; energy metabolism; energy metabolism; cyclic GMP; plasma cell; bacterial infection; SMALL INTERFERING RNA; HETERORHABDITIS; bactericidal activity; high risk behavior; Huntington chorea; Alzheimer disease; virus RNA; Immunity, Cellular; Citric Acid Cycle; guanylate cyclase; gene overexpression; RNA virus; Host-Pathogen Interactions; host pathogen interaction; Biological Evolution; host-pathogen interaction; Hemolymph; fungicidal activity; Immunity, Humoral; mosquito; Arbovirus; argonaute 2 protein; dicer; pathogen associated molecular pattern; JAK-STAT signaling; immune dysregulation; infectious agent; filamentous fungus; Cecropin; diptericin; model for human diseases; drosomycin}, year = {2020}, eissn = {1664-3224} } @article{MTMT:31690514, title = {Recent Advances in Drosophila Cellular and Humoral Innate Immunity}, url = {https://m2.mtmt.hu/api/publication/31690514}, author = {Vesala, Laura and Hultmark, Dan and Valanne, Susanna}, doi = {10.3389/fimmu.2020.598618}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {11}, unique-id = {31690514}, issn = {1664-3224}, keywords = {metabolism; BACTERIA; innate immunity; Drosophila melanogaster; humoral immunity; cellular immunity; host-pathogen interaction; model for human diseases}, year = {2020}, eissn = {1664-3224} } @article{MTMT:31686183, title = {CLP gene family, a new gene family of Cotesia vestalis bracovirus inhibits melanization of Plutella xylostella hemolymph}, url = {https://m2.mtmt.hu/api/publication/31686183}, author = {Wang, Ze-Hua and Zhou, Yue-Nan and Ye, Xi-Qian and Wu, Xiao-Tong and Yang, Pei and Shi, Min and Huang, Jian-Hua and Chen, Xue-Xin}, doi = {10.1111/1744-7917.12883}, journal-iso = {INSECT SCI}, journal = {INSECT SCIENCE}, unique-id = {31686183}, issn = {1672-9609}, abstract = {Polydnaviruses (PDVs) are obligatory symbionts of parasitoid wasps and play an important role in suppressing host immune defenses. Although PDV genes that inhibit host melanization are known in Microplitis bracovirus, the functional homologs in Cotesia bracoviruses remain unknown. Here, we find that Cotesia vestalis bracovirus (CvBV) can inhibit hemolymph melanization of its host, Plutella xylostella larvae, during the early stages of parasitization, and that overexpression of highly expressed CvBV genes reduced host phenoloxidase activity. Furthermore, CvBV-7-1 in particular reduced host phenoloxidase activity within 12 h, and the injection of anti-CvBV-7-1 antibody increased the melanization of parasitized host larvae. Further analyses showed that CvBV-7-1 and three homologs from other Cotesia bracoviruses possessed a C-terminal leucine/isoleucine-rich region and had a similar function in inhibiting melanization. Therefore, a new family of bracovirus genes was proposed and named as C-terminal Leucine/isoleucine-rich Protein (CLP). Ectopic expression of CvBV-7-1 in Drosophila hemocytes increased susceptibility to bacterial repression of melanization and reduced the melanotic encapsulation of parasitized D. melanogaster by the parasitoid Leptopilina boulardi. The formation rate of wasp pupae and the eclosion rate of C. vestalis were affected when the function of CvBV-7-1 was blocked. Our findings suggest that CLP genes from Cotesia bracoviruses encoded proteins that contain a C-terminal leucine/isoleucine-rich region and function as melanization inhibitors during the early stage of parasitization, which is important for successful parasitization.}, keywords = {immunosuppression; WASP; Plutella xylostella; Host immunity; new gene family; polydnavirus}, year = {2020}, eissn = {1744-7917} } @article{MTMT:30901165, title = {Enhancer of Polycomb and the Tip60 complex repress hematological tumor initiation by negatively regulating JAK/STAT pathway activity}, url = {https://m2.mtmt.hu/api/publication/30901165}, author = {Bailetti, Alessandro A. and Negron-Pineiro, Lenny J. and Dhruva, Vishal and Harsh, Sneh and Lu, Sean and Bosula, Aisha and Bach, Erika A.}, doi = {10.1242/dmm.038679}, journal-iso = {DIS MODEL MECH}, journal = {DISEASE MODELS & MECHANISMS}, volume = {12}, unique-id = {30901165}, issn = {1754-8403}, abstract = {Myeloproliferative neoplasms (MPNs) are clonal hematopoietic disorders that cause excessive production of myeloid cells. Most MPN patients have a point mutation in JAK2 (JAK2(V617F)), which encodes a dominant-active kinase that constitutively triggers JAK/STAT signaling. In Drosophila, this pathway is simplified, with a singleJAK, Hopscotch (Hop), and a single STAT transcription factor, Stat92E. The hop(Tumorous-lethal) [hop(Tum)] allele encodes a dominant-active kinase that induces sustained Stat92E activation. Like MPN patients, hop(Tum) mutants have significantly more myeloid cells, which form invasive tumors. Through an unbiased genetic screen, we found that heterozygosity for Enhancer of Polycomb [E(Pc)], a component of the Tip60 lysine acetyltransferase complex (also known as KAT5 in humans), significantly increased tumor burden in hopTum animals. Hematopoietic depletion of E(Pc) or other Tip60 components in an otherwise wild-type background also induced blood cell tumors. The E(Pc) tumor phenotype was dependent on JAK/STAT activity, as concomitant depletion of hop or Stat92E inhibited tumor formation. Stat92E target genes were significantly upregulated in E(Pc)-mutant myeloid cells, indicating that loss of E(Pc) activates JAK STAT signaling. Neither the hop nor Stat92E gene was upregulated upon hematopoietic E(Pc) depletion, suggesting that the regulation of the JAK STAT pathway by E(Pc) is dependent on substrates other than histones. Indeed, E(Pc) depletion significantly increased expression of Hop protein in myeloid cells. This study indicates that E(Pc) works as a tumor suppressor by attenuating Hop protein expression and ultimately JAK STAT signaling. Since loss-of-function mutations in the human homologs of E(Pc) and Tip60 are frequently observed in cancer, our work could lead to new treatments for MPN patients.This article has an associated First Person interview with the first author of the paper.}, keywords = {DROSOPHILA; Tumor suppressor; MYELOPROLIFERATIVE NEOPLASMS; TIP60; JAK/STAT; E(Pc); Melanotic tumors; Lysine acetyltransferases}, year = {2019}, eissn = {1754-8411} } @article{MTMT:30510237, title = {Drosophila as a Genetic Model for Hematopoiesis}, url = {https://m2.mtmt.hu/api/publication/30510237}, author = {Banerjee, Utpal and Girard, Juliet R. and Goins, Lauren M. and Spratford, Carrie M.}, doi = {10.1534/genetics.118.300223}, journal-iso = {GENETICS}, journal = {GENETICS}, volume = {211}, unique-id = {30510237}, issn = {0016-6731}, abstract = {In this FlyBook chapter, we present a survey of the current literature on the development of the hematopoietic system in Drosophila. The Drosophila blood system consists entirely of cells that function in innate immunity, tissue integrity, wound healing, and various forms of stress response, and are therefore functionally similar to myeloid cells in mammals. The primary cell types are specialized for phagocytic, melanization, and encapsulation functions. As in mammalian systems, multiple sites of hematopoiesis are evident in Drosophila and the mechanisms involved in this process employ many of the same molecular strategies that exemplify blood development in humans. Drosophila blood progenitors respond to internal and external stress by coopting developmental pathways that involve both local and systemic signals. An important goal of these Drosophila studies is to develop the tools and mechanisms critical to further our understanding of human hematopoiesis during homeostasis and dysfunction.}, keywords = {DROSOPHILA; innate immunity; Hematopoiesis; stress response; Lamellocyte; Hemocyte; Plasmatocyte; lymph gland; FlyBook; crystal cell}, year = {2019}, eissn = {1943-2631}, pages = {367-417} } @article{MTMT:30907377, title = {Pericardin, a Drosophila collagen, facilitates accumulation of hemocytes at the heart}, url = {https://m2.mtmt.hu/api/publication/30907377}, author = {Cevik, Duygu and Acker, Meryl and Michalski, Camilla and Jacobs, J. Roger}, doi = {10.1016/j.ydbio.2019.06.006}, journal-iso = {DEV BIOL}, journal = {DEVELOPMENTAL BIOLOGY}, volume = {454}, unique-id = {30907377}, issn = {0012-1606}, abstract = {Hematopoietic cell lineages support organismal needs by responding to positional and systemic signals that balance proliferative and differentiation events. Drosophila provides an excellent genetic model to dissect these signals, where the activity of cues in the hemolymph or substrate can be traced to determination and differentiation events of well characterized hemocyte types. Plasmatocytes in third instar larvae increase in number in response to infection and in anticipation of metamorphosis. Here we characterize hemocyte clustering, proliferation and transdifferentiation on the heart or dorsal vessel. Hemocytes accumulate on the inner foldings of the heart basement membrane, where they move with heart contraction, and are in proximity to the heart ostia and pericardial nephrocytes. The numbers of hemocytes vary, but increase transiently before pupariation, and decrease by 4 h before pupa formation. During their accumulation at the heart, plasmatocytes can proliferate and can transdifferentiate into crystal cells. Serrate expressing cells as well as lamellocyte-like, Atilla expressing ensheathing cells are associated with some, but not all hemocyte clusters. Hemocyte aggregation is enhanced by the presence of a heart specific Collagen, Pericardin, but not the associated pericardial cells. The varied and transient number of hemocytes in the pericardial compartment suggests that this is not a hematopoietic hub, but a niche supporting differentiation and rapid dispersal in response to systemic signals.}, keywords = {INFECTION; niche; extracellular matrix; Hematopoiesis; Lamellocyte; Plasmatocyte; dorsal vessel; klf15; Viking. lonely heart}, year = {2019}, eissn = {1095-564X}, pages = {52-65} } @article{MTMT:30908691, title = {The prophenoloxidase system in Drosophila participates in the anti-nematode immune response}, url = {https://m2.mtmt.hu/api/publication/30908691}, author = {Cooper, Dustin and Wuebbolt, Caitlin and Heryanto, Christa and Eleftherianos, Ioannis}, doi = {10.1016/j.molimm.2019.03.008}, journal-iso = {MOL IMMUNOL}, journal = {MOLECULAR IMMUNOLOGY}, volume = {109}, unique-id = {30908691}, issn = {0161-5890}, abstract = {Drosophila melanogaster relies on an evolutionarily conserved innate immune system to protect itself from potentially deadly pathogens. One of the earliest pathways activated after injury or infection is the melanization pathway, which is responsible for synthesizing and depositing melanin at the site of injury, or onto invading microbes. Three genes, PPO1-3, encoding prophenoloxidase (PPO), an inactive precursor of phenoloxidase (PO), are responsible for the production of melanin after their activation via immune challenge. One pathogen capable of infecting D. melanogaster are entomopathogenic nematodes. Steinernema carpocapsae nematodes exist in a mutualistic relationship with Xenorhabdus nematophila bacteria and are an important biological control agent for controlling insect pests. The nematode-bacteria complex (symbiotic nematodes) can be separated, creating "axenic" nematodes, devoid of their associated bacteria, which are still capable of infecting and killing D. melanogaster. In order to investigate how the D. melanogaster melanization pathway contributes to the anti nematode immune response, symbiotic and axenic S. carpocapsae were used to study D. melanogaster survival, PPO gene expression, and activation of PPO to PO. Our research suggests that the expression of all three D. melanogaster PPO genes contributes to survival, however only PPO1 or PPO3 appear to be up-regulated during axenic or symbiotic nematode infection. Additionally, we present data suggesting that a complex regulatory system exists between PPOs, potentially allowing for the compensation of PPOs by one another. Further, we found that axenic nematode infection leads to higher levels of PO, suggesting that X. nematophila suppresses this activation. We also report for the first time the differentiation of lamellocytes, a specialized type of hemocytes in D. melanogaster, in response to symbiotic S. carpocapsae nematode infection. Our results suggest an important role played by the melanization pathway in response to nematode infection, and demonstrate how this response can be manipulated by S. carpocapsae nematodes and their mutualistic X. nematophila bacteria.}, keywords = {DROSOPHILA; innate immunity; Steinernema; prophenoloxidase; Parasitic nematode}, year = {2019}, eissn = {1872-9142}, pages = {88-98} } @article{MTMT:30907275, title = {Drosophila Cellular Immunity Against Parasitoid Wasps: A Complex and Time-Dependent Process}, url = {https://m2.mtmt.hu/api/publication/30907275}, author = {Kim-Jo, Chami and Gatti, Jean-Luc and Poirie, Marylene}, doi = {10.3389/fphys.2019.00603}, journal-iso = {FRONT PHYSIOL}, journal = {FRONTIERS IN PHYSIOLOGY}, volume = {10}, unique-id = {30907275}, abstract = {Host-parasitoid interactions are among the most studied interactions between invertebrates because of their fundamental interest - the evolution of original traits in parasitoids - and applied, parasitoids being widely used in biological control. Immunity, and in particular cellular immunity, is central in these interactions, the host encapsulation response being specific for large foreign bodies such as parasitoid eggs. Although already well studied in this species, recent data on Drosophila melanogaster have unquestionably improved knowledge of invertebrate cellular immunity. At the same time, the venomics of parasitoids has expanded, notably those of Drosophila. Here, we summarize and discuss these advances, with a focus on an emerging "time-dependent" view of interactions outcome at the intra- and interspecific level. We also present issues still in debate and prospects for study. Data on the Drosophila-parasitoid model paves the way to new concepts in insect immunity as well as parasitoid wasp strategies to overcome it.}, keywords = {VENOM; DROSOPHILA; Immunity; encapsulation; Hematopoiesis; Parasitoid wasp; Leptopilina}, year = {2019}, eissn = {1664-042X} } @article{MTMT:30961322, title = {Expression of Human Mutant Huntingtin Protein in Drosophila Hemocytes Impairs Immune Responses}, url = {https://m2.mtmt.hu/api/publication/30961322}, author = {Lin, Yu-Hsien and Maaroufi, Houda Ouns and Ibrahim, Emad and Kucerova, Lucie and Zurovec, Michal}, doi = {10.3389/fimmu.2019.02405}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {10}, unique-id = {30961322}, issn = {1664-3224}, abstract = {The pathogenic effect of mutant HTT (mHTT) which causes Huntington disease (HD) are not restricted to nervous system. Such phenotypes include aberrant immune responses observed in the HD models. However, it is still unclear how this immune dysregulation influences the innate immune response against pathogenic infection. In the present study, we used transgenic Drosophila melanogaster expressing mutant HTT protein (mHTT) with hemocyte-specific drivers and examined the immune responses and hemocyte function. We found that mHTT expression in the hemocytes did not affect fly viability, but the numbers of circulating hemocytes were significantly decreased. Consequently, we observed that the expression of mHTT in the hemocytes compromised the immune responses including clot formation and encapsulation which lead to the increased susceptibility to entomopathogenic nematode and parasitoid wasp infections. In addition, mHTT expression in Drosophila macrophage-like S2 cells in vitro reduced ATP levels, phagocytic activity and the induction of antimicrobial peptides. Further effects observed in mHTT-expressing cells included the altered production of cytokines and activation of JAK/STAT signaling. The present study shows that the expression of mHTT in Drosophila hemocytes causes deficient cellular and humoral immune responses against invading pathogens. Our findings provide the insight into the pathogenic effects of mHTT in the immune cells.}, keywords = {PHAGOCYTOSIS; INFECTION; Cytokines; Immunity; Drosophila melanogaster; Huntington's disease; antimicrobial peptide (AMPs)}, year = {2019}, eissn = {1664-3224} } @article{MTMT:30518197, title = {Insights into the venom protein components of Microplitis mediator, an endoparasitoid wasp}, url = {https://m2.mtmt.hu/api/publication/30518197}, author = {Lin, Zhe and Wang, Rui-Juan and Cheng, Yang and Du, Jie and Volovych, Olga and Han, Li-Bin and Li, Jian-Cheng and Hu, Yang and Lu, Zi-Yun and Lu, Zhiqiang and Zou, Zhen}, doi = {10.1016/j.ibmb.2018.12.013}, journal-iso = {INSECT BIOCHEM MOLEC}, journal = {INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY}, volume = {105}, unique-id = {30518197}, issn = {0965-1748}, abstract = {Endoparasitoid wasps deliver a variety of maternal factors, such as venom proteins, viruses, and virus-like particles, from their venom and calyx fluid into hosts and thereby regulate the hosts' immune response, metabolism and development. The endoparasitoid, Microplitis mediator, is used as an important biological agent for controlling the devastating pest Helicoverpa armigera. In this study, using an integrated transcriptomic and proteomic analysis approach, we identified 75 putative venom proteins in M. mediator. The identified venom components were consistent with other known parasitoid wasps' venom proteins, including metalloproteases, serine protease inhibitors, and glycoside hydrolase family 18 enzymes. The metalloprotease and serpin family showed extensive gene duplications in venom apparatus. Isobaric tags for relative and absolute quantitation (iTRAQ) based quantitative proteomics revealed 521 proteins that were differentially expressed at 6 h and 24 h post-parasitism, including 10 wasp venom proteins that were released into the host hemolymph. Further analysis indicated that 511 differentially expressed proteins (DEP) from the host are primarily involved in the immune response, material metabolism, and extracellular matrix receptor interaction. Taken together, our results on parasitoid wasp venoms have the potential to enhance the application of endoparasitoid wasps for controlling insect pest.}, keywords = {VENOM; proteome; Serine protease inhibitor; Metalloprotease; ITRAQ; Helicoverpa armigera; Microplitis mediator}, year = {2019}, eissn = {1879-0240}, pages = {33-42} } @article{MTMT:30641961, title = {Two Nimrod receptors, NimC1 and Eater, synergistically contribute to bacterial phagocytosis in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/30641961}, author = {Melcarne, Claudia and Ramond, Elodie and Dudzic, Jan and Bretscher, Andrew and Kurucz, Judit Éva and Andó, István and Lemaitre, Bruno}, doi = {10.1111/febs.14857}, journal-iso = {FEBS J}, journal = {FEBS JOURNAL}, volume = {286}, unique-id = {30641961}, issn = {1742-464X}, year = {2019}, eissn = {1742-4658}, pages = {2670-2691}, orcid-numbers = {Andó, István/0000-0002-4648-9396} } @article{MTMT:30913672, title = {Lime is a new protein linking immunity and metabolism in Drosophila}, url = {https://m2.mtmt.hu/api/publication/30913672}, author = {Mihajlovic, Zorana and Tanasic, Dajana and Bajgar, Adam and Perez-Gomez, Raquel and Steffal, Pavel and Krejci, Alena}, doi = {10.1016/j.ydbio.2019.05.005}, journal-iso = {DEV BIOL}, journal = {DEVELOPMENTAL BIOLOGY}, volume = {452}, unique-id = {30913672}, issn = {0012-1606}, abstract = {The proliferation, differentiation and function of immune cells in vertebrates, as well as in the invertebrates, is regulated by distinct signalling pathways and crosstalk with systemic and cellular metabolism. We have identified the Lime gene (Linking Immunity and Metabolism, CG18446) as one such connecting factor, linking hemocyte development with systemic metabolism in Drosophila. Lime is expressed in larval plasmatocytes and the fat body and regulates immune cell type and number by influencing the size of hemocyte progenitor populations in the lymph gland and in circulation. Lime mutant larvae exhibit low levels of glycogen and trehalose energy reserves and they develop low number of hemocytes. The low number of hemocytes in Lime mutants can be rescued by Lime overexpression in the fat body. It is well known that immune cell metabolism is tightly regulated with the progress of infection and it must be supported by systemic metabolic changes. Here we demonstrate that Lime mutants fails to induce such systemic metabolic changes essential for the larval immune response. Indeed, Lime mutants are not able to sustain high numbers of circulating hemocytes and are compromised in the number of lamellocytes produced during immune system challenge, using a parasitic wasp infection model. We therefore propose the Lime gene as a novel functional link between systemic metabolism and Drosophila immunity.}, keywords = {metabolism; DROSOPHILA; Immunity; CG18446; Leptopilina boulardii}, year = {2019}, eissn = {1095-564X}, pages = {83-94} } @article{MTMT:30907260, title = {Lethal Interaction of Nuclear and Mitochondrial Genotypes in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/30907260}, author = {Salminen, Tiina S. and Cannino, Giuseppe and Oliveira, Marcos T. and Lillsunde, Paivi and Jacobs, Howard T. and Kaguni, Laurie S.}, doi = {10.1534/g3.119.400315}, journal-iso = {G3-GENES GENOM GENET}, journal = {G3-GENES GENOMES GENETICS}, volume = {9}, unique-id = {30907260}, issn = {2160-1836}, abstract = {Drosophila melanogaster, like most animal species, displays considerable genetic variation in both nuclear and mitochondrial DNA (mtDNA). Here we tested whether any of four natural mtDNA variants was able to modify the effect of the phenotypically mild, nuclear tko(25t) mutation, affecting mitochondrial protein synthesis. When combined with tko(25t), the mtDNA from wild strain KSA2 produced pupal lethality, accompanied by the presence of melanotic nodules in L3 larvae. KSA2 mtDNA, which carries a substitution at a conserved residue of cytochrome b that is predicted to be involved in subunit interactions within respiratory complex III, conferred drastically decreased respiratory capacity and complex III activity in the tko(25t) but not a wild-type nuclear background. The complex III inhibitor antimycin A was able to phenocopy effects of the tko(25t) mutation in the KSA2 mtDNA background. This is the first report of a lethal, nuclear-mitochondrial interaction within a metazoan species, representing a paradigm for understanding genetic interactions between nuclear and mitochondrial genotype relevant to human health and disease.}, keywords = {Respiration; Cytochrome b; MTDNA COPY NUMBER; Cybrid; melanotic nodules}, year = {2019}, eissn = {2160-1836}, pages = {2225-2234} } @article{MTMT:30901163, title = {Insect hemolymph coagulation: Kinetics of classically and non-classically secreted clotting factors}, url = {https://m2.mtmt.hu/api/publication/30901163}, author = {Schmid, Martin R. and Dziedziech, Alexis and Arefin, Badrul and Kienzle, Thomas and Wang, Zhi and Akhter, Munira and Berka, Jakub and Theopold, Ulrich}, doi = {10.1016/j.ibmb.2019.04.007}, journal-iso = {INSECT BIOCHEM MOLEC}, journal = {INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY}, volume = {109}, unique-id = {30901163}, issn = {0965-1748}, abstract = {In most insects, hemolymph coagulation, which is analogous to mammalian blood clotting, involves close collaboration between humoral and cellular components. To gain insights into the secretion of cellular clotting factors, we created tagged versions of three different clotting factors. Our focus was on factors which are released in a non-classical manner and to characterize them in comparison to a protein that is classically released, namely Glutactin (Glt). Transglutaminase-A (Tg) and Prophenoloxidase 2 (PPO2), both of which lack signal peptide sequences, have been previously demonstrated to be released from plasmatocytes and crystal cells (CCs) respectively, the two hemocyte classes in naive larvae. We found that at the molecular level, Tg secretion resembles the release of tissue transglutaminase in mammals. Specifically, Drosophila Tg is associated with vesicular membranes and remains membrane-bound after release, in contrast to Glt, which we found localizes to a different class of vesicles and is integrated into clot fibers. PPO2 on the other hand, is set free from CCs through cytolysis. We confirm that PPO2 is a central component of the cytosolic crystals and find that the distribution of PPO2 appears to vary across crystals and cells. We propose a tentative scheme for the secretory events during early and late hemolymph coagulation.}, keywords = {TRANSGLUTAMINASE; COAGULATION; SECRETION; BACTERIA; Drosophila melanogaster; Defense; Hemolymph; clotting; Wounding; prophenoloxidase; Non-classical secretion; Glutactin; Septic injury}, year = {2019}, eissn = {1879-0240}, pages = {63-71}, orcid-numbers = {Arefin, Badrul/0000-0003-1117-9125} } @article{MTMT:30509856, title = {Immune-inducible non-coding RNA molecule lincRNA-IBIN connects immunity and metabolism in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/30509856}, author = {Valanne, Susanna and Salminen, Tiina S. and Jarvela-Stolting, Mirva and Vesala, Laura and Ramet, Mika}, doi = {10.1371/journal.ppat.1007504}, journal-iso = {PLOS PATHOG}, journal = {PLOS PATHOGENS}, volume = {15}, unique-id = {30509856}, issn = {1553-7366}, abstract = {Non-coding RNAs have important roles in regulating physiology, including immunity. Here, we performed transcriptome profiling of immune-responsive genes in Drosophila melanogaster during a Gram-positive bacterial infection, concentrating on long non-coding RNA (lncRNA) genes. The gene most highly induced by a Micrococcus luteus infection was CR44404, named Induced by Infection (lincRNA-IBIN). lincRNA-IBIN is induced by both Gram-positive and Gram-negative bacteria in Drosophila adults and parasitoid wasp Leptopilina boulardi in Drosophila larvae, as well as by the activation of the Toll or the Imd pathway in unchallenged flies. We show that upon infection, lincRNA-IBIN is expressed in the fat body, in hemocytes and in the gut, and its expression is regulated by NF-B signaling and the chromatin modeling brahma complex. In the fat body, overexpression of lincRNA-IBIN affected the expression of Toll pathway -mediated genes. Notably, overexpression of lincRNA-IBIN in unchallenged flies elevated sugar levels in the hemolymph by enhancing the expression of genes important for glucose retrieval. These data show that lncRNA genes play a role in Drosophila immunity and indicate that lincRNA-IBIN acts as a link between innate immune responses and metabolism.}, year = {2019}, eissn = {1553-7374} } @article{MTMT:30585796, title = {Headcase is a Repressor of Lamellocyte Fate in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/30585796}, author = {Varga, Gergely István and Csordás, Gábor and Cinege, Gyöngyi Ilona and Jankovics, Ferenc and Sinka, Rita and Kurucz, Judit Éva and Andó, István and Honti, Viktor}, doi = {10.3390/genes10030173}, journal-iso = {GENES-BASEL}, journal = {GENES}, volume = {10}, unique-id = {30585796}, issn = {2073-4425}, abstract = {Due to the evolutionary conservation of the regulation of hematopoiesis, Drosophila provides an excellent model organism to study blood cell differentiation and hematopoietic stem cell (HSC) maintenance. The larvae of Drosophila melanogaster respond to immune induction with the production of special effector blood cells, the lamellocytes, which encapsulate and subsequently kill the invader. Lamellocytes differentiate as a result of a concerted action of all three hematopoietic compartments of the larva: the lymph gland, the circulating hemocytes, and the sessile tissue. Within the lymph gland, the communication of the functional zones, the maintenance of HSC fate, and the differentiation of effector blood cells are regulated by a complex network of signaling pathways. Applying gene conversion, mutational analysis, and a candidate based genetic interaction screen, we investigated the role of Headcase (Hdc), the homolog of the tumor suppressor HECA in the hematopoiesis of Drosophila. We found that naive loss-of-function hdc mutant larvae produce lamellocytes, showing that Hdc has a repressive role in effector blood cell differentiation. We demonstrate that hdc genetically interacts with the Hedgehog and the Decapentaplegic pathways in the hematopoietic niche of the lymph gland. By adding further details to the model of blood cell fate regulation in the lymph gland of the larva, our findings contribute to the better understanding of HSC maintenance.}, keywords = {DIFFERENTIATION; DROSOPHILA; innate immunity; blood cell; niche; Hematopoiesis; Hemocyte}, year = {2019}, eissn = {2073-4425}, orcid-numbers = {Varga, Gergely István/0000-0001-9073-5788; Csordás, Gábor/0000-0001-6871-6839; Sinka, Rita/0000-0003-4040-4184; Andó, István/0000-0002-4648-9396} } @article{MTMT:30907274, title = {Venom Atypical Extracellular Vesicles as Interspecies Vehicles of Virulence Factors Involved in Host Specificity: The Case of a Drosophila Parasitoid Wasp}, url = {https://m2.mtmt.hu/api/publication/30907274}, author = {Wan, Bin and Goguet, Emilie and Ravallec, Marc and Pierre, Olivier and Lemauf, Severine and Volkoff, Anne-Nathalie and Gatti, Jean-Luc and Poirie, Marylone}, doi = {10.3389/fimmu.2019.01688}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {10}, unique-id = {30907274}, issn = {1664-3224}, abstract = {Endoparasitoid wasps, which lay eggs inside the bodies of other insects, use various strategies to protect their offspring from the host immune response. The hymenopteran species of the genus Leptopilina, parasites of Drosophila, rely on the injection of a venom which contains proteins and peculiar vesicles (hereafter venosomes). We show here that the injection of purified L. boulardi venosomes is sufficient to impair the function of the Drosophila melanogaster lamellocytes, a hemocyte type specialized in the defense against wasp eggs, and thus the parasitic success of the wasp. These venosomes seem to have a unique extracellular biogenesis in the wasp venom apparatus where they acquire specific secreted proteins/virulence factors and act as a transport system to deliver these compounds into host lamellocytes. The level of venosomes entry into lamellocytes of different Drosophila species was correlated with the rate of parasitism success of the wasp, suggesting that this venosome-cell interaction may represent a new evolutionary level of host-parasitoid specificity.}, keywords = {DROSOPHILA; Virulence; Immunity; Lamellocyte; Parasitoid wasp; Leptopilina; venosomes}, year = {2019}, eissn = {1664-3224} } @article{MTMT:27602855, title = {Embryonic hematopoiesis modulates the inflammatory response and larval hematopoiesis in Drosophila}, url = {https://m2.mtmt.hu/api/publication/27602855}, author = {Bazzi, Wael and Cattenoz, Pierre B and Delaporte, Claude and Dasari, Vasanthi and Sakr, Rosy and Yuasa, Yoshihiro and Giangrande, Angela}, doi = {10.7554/eLife.34890.001}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {7}, unique-id = {27602855}, issn = {2050-084X}, abstract = {Recent lineage tracing analyses have significantly improved our understanding of immune system development and highlighted the importance of the different hematopoietic waves. The current challenge is to understand whether these waves interact and whether this affects the function of the immune system. Here we report a molecular pathway regulating the immune response and involving the communication between embryonic and larval hematopoietic waves in Drosophila. Down-regulating the transcription factor Gcm specific to embryonic hematopoiesis enhances the larval phenotypes induced by over-expressing the pro-inflammatory Jak/Stat pathway or by wasp infestation. Gcm works by modulating the transduction of the Upd cytokines to the site of larval hematopoiesis and hence the response to chronic Jak/Stat overexpression and acute wasp infestation immune challenges. Thus, homeostatic interactions control the function of the immune system in physiology and pathology. Our data also indicate that a transiently expressed developmental pathway has a long-lasting effect on the immune response. © Bazzi et al.}, year = {2018}, eissn = {2050-084X} } @article{MTMT:30510499, title = {From Drosophila Blood Cells to Human Leukemia}, url = {https://m2.mtmt.hu/api/publication/30510499}, author = {Boulet, Manon and Miller, Marion and Vandel, Laurence and Waltzer, Lucas}, doi = {10.1007/978-981-13-0529-0_11}, journal-iso = {ADV EXP MED BIOL}, journal = {ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY}, volume = {1076}, unique-id = {30510499}, issn = {0065-2598}, abstract = {The hematopoietic system plays a critical role in establishing the proper response against invading pathogens or in removing cancerous cells. Furthermore, deregulations of the hematopoietic differentiation program are at the origin of numerous diseases including leukemia. Importantly, many aspects of blood cell development have been conserved from human to Drosophila. Hence, Drosophila has emerged as a potent genetic model to study blood cell development and leukemia in vivo. In this chapter, we give a brief overview of the Drosophila hematopoietic system, and we provide a protocol for the dissection and the immunostaining of the larval lymph gland, the most studied hematopoietic organ in Drosophila. We then focus on the various paradigms that have been used in fly to investigate how conserved genes implicated in leukemogenesis control blood cell development. Specific examples of Drosophila models for leukemia are presented, with particular attention to the most translational ones. Finally, we discuss some limitations and potential improvements of Drosophila models for studying blood cell cancer.}, keywords = {LEUKEMIA; DROSOPHILA; SCREEN; Hematopoiesis}, year = {2018}, eissn = {2214-8019}, pages = {195-214} } @article{MTMT:30510502, title = {Jumu is required for circulating hemocyte differentiation and phagocytosis in Drosophila}, url = {https://m2.mtmt.hu/api/publication/30510502}, author = {Hao, Yangguang and Yu, Shichao and Luo, Fangzhou and Jin, Li Hua}, doi = {10.1186/s12964-018-0305-3}, journal-iso = {CELL COMM SIGN}, journal = {CELL COMMUNICATION AND SIGNALING}, volume = {16}, unique-id = {30510502}, issn = {1478-811X}, abstract = {Background: The regulatory mechanisms of hematopoiesis and cellular immunity show a high degree of similarity between insects and mammals, and Drosophila has become a good model for investigating cellular immune responses. Jumeau (Jumu) is a member of the winged-helix/forkhead (FKH) transcription factor family and is required for Drosophila development. Adult jumu mutant flies show defective hemocyte phagocytosis and a weaker defense capability against pathogen infection. Here, we further investigated the role of jumu in the regulation of larval hemocyte development and phagocytosis.}, keywords = {PHAGOCYTOSIS; DROSOPHILA; HEMOCYTES; Cytoskeleton reorganization; Jumu}, year = {2018}, eissn = {1478-811X} } @article{MTMT:30514422, title = {Time-course analysis of Drosophila suzukii interaction with endoparasitoid wasps evidences a delayed encapsulation response compared to D-melanogaster}, url = {https://m2.mtmt.hu/api/publication/30514422}, author = {Iacovone, Alessia and Ris, Nicolas and Poirie, Marylene and Gatti, Jean-Luc}, doi = {10.1371/journal.pone.0201573}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {13}, unique-id = {30514422}, issn = {1932-6203}, abstract = {Drosophila suzukii (the spotted-wing Drosophila) appears to be unsuitable for the development of most Drosophila larval endoparasitoids, be they sympatric or not. Here, we questioned the physiological bases of this widespread failure by characterizing the interactions between D. suzukii and various parasitoid species (Asobara japonica, Leptopiiina boulardi, Leptopilina heterotoma and Leptopilina victoriae) and comparing them with those observed with D. meianogaster, a rather appropriate host. All parasitoids were able to oviposit in L1 and L2 larval stages of both hosts but their propensity to parasitize was higher on D. meianogaster. A. japonica and, to a much lesser extent, L. heterotoma, were the two species able to successfully develop in D. suzukii, the failure of the parasitism resulting either in the parasitoid encapsulation (notably with L. heterotoma) or the host and parasitoid deaths (especially with L. boulardi and L. victoriae). Compared to D. meianogaster, encapsulation in D. suzukii was strongly delayed and led, if successful, to the production of much larger capsules in surviving flies and, in the event of failure, to the death of both partners because of an uncontrolled melanization. The results thus revealed a different timing of the immune response to parasitoids in D. suzukii compared to D. melanogaster with a lose-lose outcome for parasitoids (generally unsuccessful development) and hosts (high mortality and possible reduction of the fitness of survivors). Finally, these results might suggest that some European endoparasitoids of Drosophila interact with this pest in the field in an unmeasurable way, since they kill their host without reproductive success.}, year = {2018}, eissn = {1932-6203} } @article{MTMT:30510505, title = {A Metalloprotease Homolog Venom Protein From a Parasitoid Wasp Suppresses the Toll Pathway in Host Hemocytes}, url = {https://m2.mtmt.hu/api/publication/30510505}, author = {Lin, Zhe and Cheng, Yang and Wang, Rui-Juan and Du, Jie and Volovych, Olga and Li, Jian-Cheng and Hu, Yang and Lu, Zi-Yun and Lu, Zhiqiang and Zou, Zhen}, doi = {10.3389/fimmu.2018.02301}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {9}, unique-id = {30510505}, issn = {1664-3224}, abstract = {Parasitoid wasps depend on a variety of maternal virulence factors to ensure successful parasitism. Encapsulation response carried out by host hemocytes is one of the major host immune responses toward limiting endoparasitoid wasp offspring production. We found that VRF1, a metalloprotease homolog venom protein identified from the endoparasitoid wasp, Microplitis mediator, could modulate egg encapsulation in its host, the cotton bollworm, Helicoverpa armigera. Here, we show that the VRF1 proenzyme is cleaved after parasitism, and that the C-terminal fragment containing the catalytic domain enters host hemocytes 6 h post-parasitism. Furthermore, using yeast two-hybrid and pull-down assays, VRF1 is shown to interact with the H. armigera NF-kappa B factor, Dorsal. We also show that overexpressed of VRF1 in an H. armigera cell line cleaved Dorsal in vivo. Taken together, our results have revealed a novel mechanism by which a component of endoparasitoid wasp venom interferes with the Toll signaling pathway in the host hemocytes.}, keywords = {VENOM; Metalloprotease; Helicoverpa armigera; Toll pathway; Microplitis mediator}, year = {2018}, eissn = {1664-3224} } @article{MTMT:31149601, title = {Detecting proliferation of adult hemocytes in Drosophila by BrdU incorporation [version 1; referees: 2 approved]}, url = {https://m2.mtmt.hu/api/publication/31149601}, author = {Mandal, L. and Ghosh, S. and Mandal, S.}, doi = {10.12688/wellcomeopenres.14560.1}, journal-iso = {WELLCOME OPEN RESEARCH}, journal = {WELLCOME OPEN RESEARCH}, volume = {3}, unique-id = {31149601}, issn = {2398-502X}, abstract = {Drosophila and mammalian hematopoiesis share several similarities that ranges from phases to the battery of transcription factors and signaling molecules that execute this process. These resounding similarities along with the rich genetic tools available in fruitfly makes it a popular invertebrate model to study blood cell development both during normal and aberrant conditions. The larval system is the most extensively studied to date. Several studies have shown that these hemocytes just like mammalian counterpart proliferate and get routinely regenerated upon infection. However, employing the same protocol it was concluded that blood cell proliferation although abundant in larval stages is absent in adult fruitfly. The current protocol describes the strategies that can be employed to document the hemocyte proliferation in adulthood. The fact that a subset of blood cells tucked away in the hematopoietic hub are not locked in senescence, rather they still harbour the proliferative capacity to tide over challenges was successfully demonstrated by this method. Although we have adopted bacterial infection as a bait to evoke this proliferative capacity of the hemocytes, we envision that it can also efficiently characterize the proliferative responses of hemocytes in tumorigenic conditions as well as scenarios of environmental and metabolic stresses during adulthood. © 2018 Ghosh S et al.}, keywords = {INFECTION; PROLIFERATION; MACROPHAGE; Hematopoiesis; Adult Drosophila}, year = {2018} } @article{MTMT:30518205, title = {Innate Immune Memory in Invertebrate Metazoans: A Critical Appraisal}, url = {https://m2.mtmt.hu/api/publication/30518205}, author = {Melillo, Daniela and Marino, Rita and Italiani, Paola and Boraschi, Diana}, doi = {10.3389/fimmu.2018.01915}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {9}, unique-id = {30518205}, issn = {1664-3224}, abstract = {The ability of developing immunological memory, a characteristic feature of adaptive immunity, is clearly present also in innate immune responses. In fact, it is well known that plants and invertebrate metazoans, which only have an innate immune system, can mount a faster and more effective response upon re-exposure to a stimulus. Evidence of immune memory in invertebrates comes from studies in infection immunity, natural transplantation immunity, individual, and transgenerational immune priming. These studies strongly suggest that environment and lifestyle take part in the development of immunological memory. However, in several instances the formal correlation between the phenomenon of immune memory and molecular and functional immune parameters is stillmissing. In this review, we have critically examined the cellular and humoral aspects of the invertebrate immune memory responses. In particular, we have focused our analysis on studies that have addressed immune memory in the most restrictive meaning of the term, i.e., the response to a challenge of a quiescent immune system that has been primed in the past. These studies highlight the central role of an increase in the number of immune cells and of their epigenetic re-programming in the establishment of sensu stricto immune memory in invertebrates.}, keywords = {innate immunity; invertebrates; immunological memory; immune priming; innate memory}, year = {2018}, eissn = {1664-3224} } @article{MTMT:27524974, title = {Morphological characterization of hemocyte types in some species belonging to Tettigoniidae and Pamphagidae (Insecta: Orthoptera)}, url = {https://m2.mtmt.hu/api/publication/27524974}, author = {Ozturk, Gurhan and Cakici, Ozlem and Arikan, Huseyin}, doi = {10.3906/zoo-1711-11}, journal-iso = {TURK J ZOOL}, journal = {TURKISH JOURNAL OF ZOOLOGY}, volume = {42}, unique-id = {27524974}, issn = {1300-0179}, year = {2018}, eissn = {1303-6114}, pages = {340-345} } @article{MTMT:27602854, title = {Mechanical stress to Drosophila larvae stimulates a cellular immune response through the JAK/STAT signaling pathway}, url = {https://m2.mtmt.hu/api/publication/27602854}, author = {Tokusumi, Yumiko and Tokusumi, Tsuyoshi and Schulz, Robert A}, doi = {10.1016/j.bbrc.2018.05.192}, journal-iso = {BIOCHEM BIOPH RES CO}, journal = {BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS}, volume = {502}, unique-id = {27602854}, issn = {0006-291X}, year = {2018}, eissn = {1090-2104}, pages = {415-421}, orcid-numbers = {Tokusumi, Tsuyoshi/0000-0001-9494-1888} } @article{MTMT:27602652, title = {Commentary: Drosophila GATA Factor Serpent Establishes Phagocytic Ability of Embryonic Macrophages}, url = {https://m2.mtmt.hu/api/publication/27602652}, author = {Valanne, Susanna and Vesala, Laura and Ramet, Mika}, doi = {10.3389/fimmu.2018.01582}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {9}, unique-id = {27602652}, issn = {1664-3224}, year = {2018}, eissn = {1664-3224} } @article{MTMT:26714387, title = {The Immune Phenotype of Three Drosophila Leukemia Models}, url = {https://m2.mtmt.hu/api/publication/26714387}, author = {Arefin, Badrul and Kunc, Martin and Krautz, Robert and Theopold, Ulrich}, doi = {10.1534/g3.117.039487}, journal-iso = {G3-GENES GENOM GENET}, journal = {G3-GENES GENOMES GENETICS}, volume = {7}, unique-id = {26714387}, issn = {2160-1836}, year = {2017}, eissn = {2160-1836}, pages = {2139-2149} } @article{MTMT:31149602, title = {Dscam1 in pancrustacean immunity: Current status and a look to the future}, url = {https://m2.mtmt.hu/api/publication/31149602}, author = {Armitage, S.A.O. and Kurtz, J. and Brites, D. and Dong, Y. and Pasquier, L.D. and Wang, H.-C.}, doi = {10.3389/fimmu.2017.00662}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {8}, unique-id = {31149602}, issn = {1664-3224}, abstract = {The Down syndrome cell adhesion molecule 1 (Dscam1) gene is an extraordinary example of diversity: by combining alternatively spliced exons, thousands of isoforms can be produced from just one gene. So far, such diversity in this gene has only been found in insects and crustaceans, and its essential part in neural wiring has been well-characterized for Drosophila melanogaster. Ten years ago evidence from D. melanogaster showed that the Dscam1 gene is involved in insect immune defense and work on Anopheles gambiae indicated that it is a hypervariable immune receptor. These exciting findings showed that via processes of somatic diversification insects have the possibility to produce unexpected immune molecule diversity, and it was hypothesized that Dscam1 could provide the mechanistic underpinnings of specific immune responses. Since these first publications the quest to understand the function of this gene has uncovered fascinating insights from insects and crustaceans. However, we are still far from a complete understanding of how Dscam1 functions in relation to parasites and pathogens and its full relevance for the immune system. In this Hypothesis and Theory article, we first briefly introduce Dscam1 and what we know so far about how it might function in immunity. By focusing on seven questions, we then share our sometimes contrasting thoughts on what the evidence tells us so far, what essential experiments remain to be done, and the future prospects, with the aim to provide a multiangled view on what this fascinating gene has to do with immune defense. © 2017 Armitage, Kurtz, Brites, Dong, Du Pasquier and Wang.}, keywords = {GENE; PHAGOCYTOSIS; ARTICLE; IMMUNOGLOBULIN; INSECTS; PHYLOGENY; Genetic variability; innate immunity; innate immunity; gene mutation; epitope; nonhuman; Nervous System; Alternative Splicing; Gene Expression; Drosophila melanogaster; Histocompatibility; immune response; gene function; cell adhesion molecule; opsonin; microbial immunity; gene duplication; alternative RNA splicing; immunological memory; Crustaceans; immunoglobulin domain; immunoglobulin domain; White spot syndrome virus; immunoreceptor tyrosine based activation motif; Isoform diversity; protein structure, function and variability; Down syndrome cell adhesion molecule 1 gene}, year = {2017}, eissn = {1664-3224} } @article{MTMT:27260897, title = {Reactive oxygen species-dependent Toll/NF-kappa B activation in the Drosophila hematopoietic niche confers resistance to wasp parasitism}, url = {https://m2.mtmt.hu/api/publication/27260897}, author = {Louradour, Isabelle and Sharma, Anurag and Morin-Poulard, Ismael and Letourneau, Manon and Vincent, Alain and Crozatier, Michele and Vanzo, Nathalie}, doi = {10.7554/eLife.25496}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {6}, unique-id = {27260897}, issn = {2050-084X}, year = {2017}, eissn = {2050-084X} } @article{MTMT:26698808, title = {A Drosophila model of myeloproliferative neoplasm reveals a feed-forward loop in the JAK pathway mediated by p38 MAPK signalling}, url = {https://m2.mtmt.hu/api/publication/26698808}, author = {Terriente-Felix, Ana and Perez, Lidia and Bray, Sarah J and Nebreda, Angel R and Milan, Marco}, doi = {10.1242/dmm.028118}, journal-iso = {DIS MODEL MECH}, journal = {DISEASE MODELS & MECHANISMS}, volume = {10}, unique-id = {26698808}, issn = {1754-8403}, year = {2017}, eissn = {1754-8411}, pages = {399-407}, orcid-numbers = {Milan, Marco/0000-0002-7111-6444} } @article{MTMT:26698807, title = {The nociception genes painless and Piezo are required for the cellular immune response of Drosophila larvae to wasp parasitization}, url = {https://m2.mtmt.hu/api/publication/26698807}, author = {Tokusumi, Yumiko and Tokusumi, Tsuyoshi and Schulz, Robert A}, doi = {10.1016/j.bbrc.2017.03.116}, journal-iso = {BIOCHEM BIOPH RES CO}, journal = {BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS}, volume = {486}, unique-id = {26698807}, issn = {0006-291X}, year = {2017}, eissn = {1090-2104}, pages = {893-897} } @article{MTMT:26698809, title = {Macrophage Functions in Tissue Patterning and Disease: New Insights from the Fly}, url = {https://m2.mtmt.hu/api/publication/26698809}, author = {Wood, Will and Martin, Paul}, doi = {10.1016/j.devcel.2017.01.001}, journal-iso = {DEV CELL}, journal = {DEVELOPMENTAL CELL}, volume = {40}, unique-id = {26698809}, issn = {1534-5807}, year = {2017}, eissn = {1878-1551}, pages = {221-233}, orcid-numbers = {Martin, Paul/0000-0002-2665-5086} } @article{MTMT:27260896, title = {Drosophila muscles regulate the immune response against wasp infection via carbohydrate metabolism}, url = {https://m2.mtmt.hu/api/publication/27260896}, author = {Yang, Hairu and Hultmark, Dan}, doi = {10.1038/s41598-017-15940-2}, journal-iso = {SCI REP}, journal = {SCIENTIFIC REPORTS}, volume = {7}, unique-id = {27260896}, issn = {2045-2322}, year = {2017}, eissn = {2045-2322}, orcid-numbers = {Hultmark, Dan/0000-0002-6506-5855} }