@article{MTMT:34261481, title = {Anti-Tumor Effect of Turandot Proteins Induced via the JAK/STAT Pathway in the mxc Hematopoietic Tumor Mutant in Drosophila}, url = {https://m2.mtmt.hu/api/publication/34261481}, author = {Kinoshita, Yuriko and Shiratsuchi, Naoka and Araki, Mayo and Inoue, Yoshihiro H.}, doi = {10.3390/cells12162047}, journal-iso = {CELLS-BASEL}, journal = {CELLS}, volume = {12}, unique-id = {34261481}, abstract = {Several antimicrobial peptides suppress the growth of lymph gland (LG) tumors in Drosophila multi sex comb (mxc) mutant larvae. The activity of another family of polypeptides, called Turandots, is also induced via the JAK/STAT pathway after bacterial infection; however, their influence on Drosophila tumors remains unclear. The JAK/STAT pathway was activated in LG tumors, fat body, and circulating hemocytes of mutant larvae. The mRNA levels of Turandot (Tot) genes increased markedly in the mutant fat body and declined upon silencing Stat92E in the fat body, indicating the involvement of the JAK/STAT pathway. Furthermore, significantly enhanced tumor growth upon a fat-body-specific silencing of the mRNAs demonstrated the antitumor effects of these proteins. The proteins were found to be incorporated into small vesicles in mutant circulating hemocytes (as previously reported for several antimicrobial peptides) but not normal cells. In addition, more hemocytes containing these proteins were found to be associated with tumors. The mutant LGs contained activated effector caspases, and a fat-body-specific silencing of Tots inhibited apoptosis and increased the number of mitotic cells in the LG, thereby suggesting that the proteins inhibited tumor cell proliferation. Thus, Tot proteins possibly exhibit antitumor effects via the induction of apoptosis and inhibition of cell proliferation.}, keywords = {APOPTOSIS; DROSOPHILA; antitumor; JAK/STAT; Mxc; Turandots}, year = {2023}, eissn = {2073-4409} } @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:32524824, title = {Broad Ultrastructural and Transcriptomic Changes Underlie the Multinucleated Giant Hemocyte Mediated Innate Immune Response against Parasitoids}, url = {https://m2.mtmt.hu/api/publication/32524824}, author = {Cinege, Gyöngyi Ilona and Magyar, Lilla Brigitta and Kovács, Attila Lajos and Lerner, Zita and Juhász, Gábor and Lukacsovich, David and Winterer, Jochen and Lukacsovich, Tamás and Hegedűs, Zoltán and Kurucz, Judit Éva and Hultmark, Dan and Földy, Csaba and Andó, István}, doi = {10.1159/000520110}, journal-iso = {J INNATE IMMUN}, journal = {JOURNAL OF INNATE IMMUNITY}, volume = {14}, unique-id = {32524824}, issn = {1662-811X}, year = {2022}, eissn = {1662-8128}, pages = {335-354}, orcid-numbers = {Juhász, Gábor/0000-0001-8548-8874; Winterer, Jochen/0000-0002-6800-6594; Lukacsovich, Tamás/0000-0001-5908-9861; Hultmark, Dan/0000-0002-6506-5855; Andó, István/0000-0002-4648-9396} } @article{MTMT:32876826, title = {Hemocyte Clusters Defined by scRNA-Seq in Bombyx mori: In Silico Analysis of Predicted Marker Genes and Implications for Potential Functional Roles}, url = {https://m2.mtmt.hu/api/publication/32876826}, author = {Feng, M. and Swevers, L. and Sun, J.}, doi = {10.3389/fimmu.2022.852702}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {13}, unique-id = {32876826}, issn = {1664-3224}, abstract = {Within the hemolymph, insect hemocytes constitute a heterogeneous population of macrophage-like cells that play important roles in innate immunity, homeostasis and development. Classification of hemocytes in different subtypes by size, morphology and biochemical or immunological markers has been difficult and only in Drosophila extensive genetic analysis allowed the construction of a coherent picture of hemocyte differentiation from pro-hemocytes to granulocytes, crystal cells and plasmatocytes. However, the advent of high-throughput single cell technologies, such as single cell RNA sequencing (scRNA-seq), is bound to have a high impact on the study of hemocytes subtypes and their phenotypes in other insects for which a sophisticated genetic toolbox is not available. Instead of averaging gene expression across all cells as occurs in bulk-RNA-seq, scRNA-seq allows high-throughput and specific visualization of the differentiation status of individual cells. With scRNA-seq, interesting cell types can be identified in heterogeneous populations and direct analysis of rare cell types is possible. Next to its ability to profile the transcriptomes of individual cells in tissue samples, scRNA-seq can be used to propose marker genes that are characteristic of different hemocyte subtypes and predict their functions. In this perspective, the identities of the different marker genes that were identified by scRNA-seq analysis to define 13 distinct cell clusters of hemocytes in larvae of the silkworm, Bombyx mori, are discussed in detail. The analysis confirms the broad division of hemocytes in granulocytes, plasmatocytes, oenocytoids and perhaps spherulocytes but also reveals considerable complexity at the molecular level and highly specialized functions. In addition, predicted hemocyte marker genes in Bombyx generally show only limited convergence with the genes that are considered characteristic for hemocyte subtypes in Drosophila. Copyright © 2022 Feng, Swevers and Sun.}, keywords = {Animals; PHAGOCYTOSIS; FIBRINOGEN RECEPTOR; PHENOTYPE; GENETICS; TRANSCRIPTION FACTOR; ARTICLE; IMMUNOGLOBULIN; DROSOPHILA; DROSOPHILA; HEMOCYTES; animal; Cell Differentiation; MACROPHAGE; Carbohydrate; amino acid sequence; genetic analysis; innate immunity; ANTIOXIDANT; nonhuman; ribosome RNA; Aerobic metabolism; serotonin receptor; MYC PROTEIN; Wound healing; biological marker; Chromatin Assembly and Disassembly; Gene Expression; lipid metabolism; Homeostasis; Tumor Necrosis Factor; messenger rna; granulocyte; humoral immunity; blood cell; blood cell; Golgi complex; glycosylation; antioxidant activity; reactive oxygen metabolite; heat shock protein; mitochondrion; plasma cell; phosphatidylinositol 3 kinase; systematic review; microarray analysis; follow up; Microtubule; interleukin 1beta; sodium chloride; BIOGENESIS; beta Catenin; computer model; metamorphosis; Aquaporin; Transcriptome; interleukin 1beta converting enzyme; nervous system development; cathepsin B; carboxylesterase; 3' untranslated region; marker gene; marker gene; thioredoxin; beta alanine; Notch receptor; Notch signaling; Hemolymph; polypeptide antibiotic agent; beta1 integrin; alpha3 integrin; metalloproteinase inhibitor; Wnt protein; Hemocyte; thyroid hormone receptor; glucuronosyltransferase; reduced nicotinamide adenine dinucleotide dehydrogenase (ubiquinone); Single-Cell Analysis; single cell analysis; RNA-Seq; HETERODIMERIZATION; peptidylprolyl isomerase; apolipoprotein D; Pattern recognition receptor; fk 506 binding protein; alpha crystallin; White spot syndrome virus; aerobic glycolysis; gene expression level; beta3 integrin; ubiquinone; pyrimidine; nucleolin; Silkworm; Bombyx mori; Bombyx mori; peptidoglycan recognition protein; ScRNA-seq; Extracellular signaling; Baculoviridae; Nitrilase; canonical Wnt signaling; cecropin B; Bombyx; Bombyx; farnesyl diphosphate; scavenger receptor C; transcription factor RUNX; Bombyx mori nucleopolyhedrovirus; Oxidative stress; single cell RNA seq; protein p35; baculoviral IAP repeat containing protein 2}, year = {2022}, eissn = {1664-3224} } @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: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:32006062, title = {Toward a Consensus in the Repertoire of Hemocytes Identified in Drosophila}, url = {https://m2.mtmt.hu/api/publication/32006062}, author = {Cattenoz, P.B. and Monticelli, S. and Pavlidaki, A. and Giangrande, A.}, doi = {10.3389/fcell.2021.643712}, journal-iso = {FRONT CELL DEV BIOL}, journal = {FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY}, volume = {9}, unique-id = {32006062}, issn = {2296-634X}, abstract = {The catalog of the Drosophila immune cells was until recently limited to three major cell types, based on morphology, function and few molecular markers. Three recent single cell studies highlight the presence of several subgroups, revealing a large diversity in the molecular signature of the larval immune cells. Since these studies rely on somewhat different experimental and analytical approaches, we here compare the datasets and identify eight common, robust subgroups associated to distinct functions such as proliferation, immune response, phagocytosis or secretion. Similar comparative analyses with datasets from different stages and tissues disclose the presence of larval immune cells resembling embryonic hemocyte progenitors and the expression of specific properties in larval immune cells associated with peripheral tissues. © Copyright © 2021 Cattenoz, Monticelli, Pavlidaki and Giangrande.}, keywords = {PHAGOCYTOSIS; ARTICLE; DROSOPHILA; DROSOPHILA; MACROPHAGE; MACROPHAGE; innate immunity; innate immunity; nonhuman; cell proliferation; embryo; Consensus; human cell; immunocompetent cell; Lamellocyte; single cell RNA seq; single cell RNA seq}, year = {2021}, eissn = {2296-634X} } @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: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:32601905, title = {Intermediate progenitor cells provide a transition between hematopoietic progenitors and their differentiated descendants}, url = {https://m2.mtmt.hu/api/publication/32601905}, author = {Spratford, C.M. and Goins, L.M. and Chi, F. and Girard, J.R. and Macias, S.N. and Ho, V.W. and Banerjee, U.}, doi = {10.1242/dev.200216}, journal-iso = {DEVELOPMENT}, journal = {DEVELOPMENT}, volume = {148}, unique-id = {32601905}, issn = {0950-1991}, abstract = {Genetic and genomic analysis in Drosophila suggests that hematopoietic progenitors likely transition into terminal fates via intermediate progenitors (IPs) with some characteristics of either, but perhaps maintaining IP-specific markers. In the past, IPs have not been directly visualized and investigated owing to lack of appropriate genetic tools. Here, we report a Split GAL4 construct, CHIZ-GAL4, that identifies IPs as cells physically juxtaposed between true progenitors and differentiating hemocytes. IPs are a distinct cell type with a unique cell-cycle profile and they remain multipotent for all blood cell fates. In addition, through their dynamic control of the Notch ligand Serrate, IPs specify the fate of direct neighbors. The Ras pathway controls the number of IP cells and promotes their transition into differentiating cells. This study suggests that it would be useful to characterize such intermediate populations of cells in mammalian hematopoietic systems. © 2021. Published by The Company of Biologists Ltd}, keywords = {DROSOPHILA; Hematopoiesis; Blood cell development; crystal cells; Intermediate progenitor; Split GAL4}, year = {2021}, eissn = {1477-9129} } @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: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: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: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:31470141, title = {The Venom of the Ectoparasitoid WaspPachycrepoideus vindemiae(Hymenoptera: Pteromalidae) Induces Apoptosis ofDrosophila melanogasterHemocytes}, url = {https://m2.mtmt.hu/api/publication/31470141}, author = {Wan, Bin and Yang, Lei and Zhang, Jiao and Qiu, Liming and Fang, Qi and Yao, Hongwei and Poirie, Marylene and Gatti, Jean-Luc and Ye, Gongyin}, doi = {10.3390/insects11060363}, journal-iso = {INSECTS}, journal = {INSECTS}, volume = {11}, unique-id = {31470141}, abstract = {The pupal ectoparasitoidPachycrepoideus vindemiaeinjects venom into its fly hosts prior to oviposition. We have shown that this venom causes immune suppression inDrosophila melanogasterpupa but the mechanism involved remained unclear. Here, we show using transgenicD. melanogasterwith fluorescent hemocytes that the in vivo number of plasmatocytes and lamellocytes decreases after envenomation while it has a limited effect on crystal cells. After in vitro incubation with venom, the cytoskeleton of plasmatocytes underwent rearrangement with actin aggregation around the internal vacuoles, which increased with incubation time and venom concentration. The venom also decreased the lamellocytes adhesion capacity and induced nucleus fragmentation. Electron microscopy observation revealed that the shape of the nucleus and mitochondria became irregular after in vivo incubation with venom and confirmed the increased vacuolization with the formation of autophagosomes-like structures. Almost all venom-treated hemocytes became positive for TUNEL assays, indicating massive induced apoptosis. In support, the caspase inhibitor Z-VAD-FMK attenuated the venom-induced morphological changes suggesting an involvement of caspases. Our data indicate thatP. vindemiaevenom inhibitsD. melanogasterhost immunity by inducing strong apoptosis in hemocytes. These assays will help identify the individual venom component(s) responsible and the precise mechanism(s)/pathway(s) involved.}, keywords = {APOPTOSIS; VENOM; Drosophila melanogaster; cell immunity; ectoparasitoid; Pachycrepoideus vindemiae}, year = {2020}, eissn = {2075-4450} } @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: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:3096913, title = {Transdifferentiation and Proliferation in Two Distinct Hemocyte Lineages in Drosophila melanogaster Larvae after Wasp Infection.}, url = {https://m2.mtmt.hu/api/publication/3096913}, author = {Anderl, I and Vesala, L and Ihalainen, TO and Vanha-Aho, LM and Andó, István and Ramet, M and Hultmark, D}, doi = {10.1371/journal.ppat.1005746}, journal-iso = {PLOS PATHOG}, journal = {PLOS PATHOGENS}, volume = {12}, unique-id = {3096913}, issn = {1553-7366}, abstract = {Cellular immune responses require the generation and recruitment of diverse blood cell types that recognize and kill pathogens. In Drosophila melanogaster larvae, immune-inducible lamellocytes participate in recognizing and killing parasitoid wasp eggs. However, the sequence of events required for lamellocyte generation remains controversial. To study the cellular immune system, we developed a flow cytometry approach using in vivo reporters for lamellocytes as well as for plasmatocytes, the main hemocyte type in healthy larvae. We found that two different blood cell lineages, the plasmatocyte and lamellocyte lineages, contribute to the generation of lamellocytes in a demand-adapted hematopoietic process. Plasmatocytes transdifferentiate into lamellocyte-like cells in situ directly on the wasp egg. In parallel, a novel population of infection-induced cells, which we named lamelloblasts, appears in the circulation. Lamelloblasts proliferate vigorously and develop into the major class of circulating lamellocytes. Our data indicate that lamellocyte differentiation upon wasp parasitism is a plastic and dynamic process. Flow cytometry with in vivo hemocyte reporters can be used to study this phenomenon in detail.}, year = {2016}, eissn = {1553-7374}, pages = {e1005746}, orcid-numbers = {Andó, István/0000-0002-4648-9396} } @article{MTMT:26377211, title = {The Drosophila CD36 Homologue croquemort Is Required to Maintain Immune and Gut Homeostasis during Development and Aging}, url = {https://m2.mtmt.hu/api/publication/26377211}, author = {Guillou, Aurelien and Troha, Katia and Wang, Hui and Franc, Nathalie C and Buchon, Nicolas}, doi = {10.1371/journal.ppat.1005961}, journal-iso = {PLOS PATHOG}, journal = {PLOS PATHOGENS}, volume = {12}, unique-id = {26377211}, issn = {1553-7366}, year = {2016}, eissn = {1553-7374}, orcid-numbers = {Buchon, Nicolas/0000-0003-3636-8387} } @article{MTMT:3045263, title = {The raspberry Gene Is Involved in the Regulation of the Cellular Immune Response in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/3045263}, author = {Kari, Beáta and Csordás, Gábor and Honti, Viktor and Cinege, Gyöngyi Ilona and Williams, MJ and Andó, István and Kurucz, Judit Éva}, doi = {10.1371/journal.pone.0150910}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {11}, unique-id = {3045263}, issn = {1932-6203}, abstract = {Drosophila is an extremely useful model organism for understanding how innate immune mechanisms defend against microbes and parasitoids. Large foreign objects trigger a potent cellular immune response in Drosophila larva. In the case of endoparasitoid wasp eggs, this response includes hemocyte proliferation, lamellocyte differentiation and eventual encapsulation of the egg. The encapsulation reaction involves the attachment and spreading of hemocytes around the egg, which requires cytoskeletal rearrangements, changes in adhesion properties and cell shape, as well as melanization of the capsule. Guanine nucleotide metabolism has an essential role in the regulation of pathways necessary for this encapsulation response. Here, we show that the Drosophila inosine 5'-monophosphate dehydrogenase (IMPDH), encoded by raspberry (ras), is centrally important for a proper cellular immune response against eggs from the parasitoid wasp Leptopilina boulardi. Notably, hemocyte attachment to the egg and subsequent melanization of the capsule are deficient in hypomorphic ras mutant larvae, which results in a compromised cellular immune response and increased survival of the parasitoid.}, keywords = {PHAGOCYTOSIS; INHIBITORS; ACTIVATION; SCREEN; RHO; Hematopoiesis; INOSINE MONOPHOSPHATE DEHYDROGENASE; Parasitoids; SMALL GTPASES; LEPTOPILINA-BOULARDI}, year = {2016}, eissn = {1932-6203}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839; Andó, István/0000-0002-4648-9396} } @article{MTMT:2993019, title = {Innate immunity}, url = {https://m2.mtmt.hu/api/publication/2993019}, author = {Honti, Viktor and Kurucz, Judit Éva and Cinege, Gyöngyi Ilona and Csordás, Gábor and Andó, István}, journal-iso = {ACTA BIOL SZEGED}, journal = {ACTA BIOLOGICA SZEGEDIENSIS}, volume = {59}, unique-id = {2993019}, issn = {1588-385X}, year = {2015}, eissn = {1588-4082}, pages = {1-15}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839; Andó, István/0000-0002-4648-9396} } @article{MTMT:24797539, title = {Genetic dissection of leukemia-associated IDH1 and IDH2 mutants and D-2-hydroxyglutarate in Drosophila}, url = {https://m2.mtmt.hu/api/publication/24797539}, author = {Reitman, Zachary J and Sinenko, Sergey A and Spana, Eric P and Yan, Hai}, doi = {10.1182/blood-2014-05-577940}, journal-iso = {BLOOD}, journal = {BLOOD}, volume = {125}, unique-id = {24797539}, issn = {0006-4971}, year = {2015}, eissn = {1528-0020}, pages = {336-345} } @article{MTMT:2708773, title = {In Vivo Immunostaining of Hemocyte Compartments in Drosophila for Live Imaging}, url = {https://m2.mtmt.hu/api/publication/2708773}, author = {Csordás, Gábor and Varga, Gergely István and Honti, Viktor and Jankovics, Ferenc and Kurucz, Judit Éva and Andó, István}, doi = {10.1371/journal.pone.0098191}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {9}, unique-id = {2708773}, issn = {1932-6203}, abstract = {In recent years, Drosophila melanogaster has become an attractive model organism in which to study the structure and development of the cellular immune components. The emergence of immunological markers greatly accelerated the identification of the immune cells (hemocytes), while the creation of genetic reporter constructs allowed unique insight into the structural organization of hematopoietic tissues. However, investigation of the hemocyte compartments by the means of immunological markers requires dissection and fixation, which regularly disrupt the delicate structure and hamper the microanatomical characterization. Moreover, the investigation of transgenic reporters alone can be misleading as their expression often differs from the native expression pattern of their respective genes. We describe here a method that combines the reporter constructs and the immunological tools in live imaging, thereby allowing use of the array of available immunological markers while retaining the structural integrity of the hematopoietic compartments. The procedure allows the reversible immobilization of Drosophila larvae for high-resolution confocal imaging and the time-lapse video analysis of in vivo reporters. When combined with our antibody injection-based in situ immunostaining assay, the resulting double labeling of the hemocyte compartments can provide new information on the microanatomy and functional properties of the hematopoietic tissues in an intact state. Although this method was developed to study the immune system of Drosophila melanogaster, we anticipate that such a combination of genetic and immunological markers could become a versatile technique for in vivo studies in other biological systems too.}, year = {2014}, eissn = {1932-6203}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839; Varga, Gergely István/0000-0001-9073-5788; Andó, István/0000-0002-4648-9396} } @article{MTMT:24399547, title = {Drosophila hematopoiesis: Markers and methods for molecular genetic analysis}, url = {https://m2.mtmt.hu/api/publication/24399547}, author = {Evans, CJ and Liu, T and Banerjee, U}, doi = {10.1016/j.ymeth.2014.02.038}, journal-iso = {METHODS}, journal = {METHODS}, volume = {68}, unique-id = {24399547}, issn = {1046-2023}, year = {2014}, eissn = {1095-9130}, pages = {242-251} } @article{MTMT:2372553, title = {The cell-mediated immunity of Drosophila melanogaster: Hemocyte lineages, immune compartments, microanatomy and regulation.}, url = {https://m2.mtmt.hu/api/publication/2372553}, author = {Honti, Viktor and Csordás, Gábor and Kurucz, Judit Éva and Márkus, Róbert and Andó, István}, doi = {10.1016/j.dci.2013.06.005}, journal-iso = {DEV COMP IMMUNOL}, journal = {DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY}, volume = {42}, unique-id = {2372553}, issn = {0145-305X}, abstract = {In the animal kingdom, innate immunity is the first line of defense against invading pathogens. The dangers of microbial and parasitic attacks are countered by similar mechanisms, involving the prototypes of the cell-mediated immune responses, the phagocytosis and encapsulation. Work on Drosophila has played an important role in promoting an understanding of the basic mechanisms of phylogenetically conserved modules of innate immunity. The aim of this review is to survey the developments in the identification and functional definition of immune cell types and the immunological compartments of Drosophila melanogaster. We focus on the molecular and developmental aspects of the blood cell types and compartments, as well as the dynamics of blood cell development and the immune response. Further advances in the characterization of the innate immune mechanisms in Drosophila will provide basic clues to the understanding of the importance of the evolutionary conserved mechanisms of innate immune defenses in the animal kingdom.}, year = {2014}, eissn = {1879-0089}, pages = {47-56}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839; Andó, István/0000-0002-4648-9396} } @article{MTMT:24783909, title = {A role for nematocytes in the cellular immune response of the Drosophilid Zaprionus indianus}, url = {https://m2.mtmt.hu/api/publication/24783909}, author = {Kacsoh, BZ and Bozler, J and Schlenke, TA}, doi = {10.1017/S0031182013001431}, journal-iso = {PARASITOLOGY}, journal = {PARASITOLOGY}, volume = {141}, unique-id = {24783909}, issn = {0031-1820}, year = {2014}, eissn = {1469-8161}, pages = {697-715} } @article{MTMT:24854315, title = {Activation of Drosophila hemocyte motility by the ecdysone hormone}, url = {https://m2.mtmt.hu/api/publication/24854315}, author = {Sampson, Christopher J and Amin, Unum and Couso, Juan-Pablo}, doi = {10.1242/bio.20136619}, journal-iso = {BIOL OPEN}, journal = {BIOLOGY OPEN}, volume = {2}, unique-id = {24854315}, issn = {2046-6390}, year = {2013}, eissn = {2046-6390}, pages = {1412-1420} } @article{MTMT:2326115, title = {Drosophila Nimrod proteins bind bacteria}, url = {https://m2.mtmt.hu/api/publication/2326115}, author = {Zsámboki, János and Csordás, Gábor and Honti, Viktor and Pintér, Lajos and Bajusz, Izabella and Galgóczi, László Norbert and Andó, István and Kurucz, Judit Éva}, doi = {10.2478/s11535-013-0183-4}, journal-iso = {CENT EUR J BIOL}, journal = {CENTRAL EUROPEAN JOURNAL OF BIOLOGY}, volume = {8}, unique-id = {2326115}, issn = {1895-104X}, abstract = {Engulfment of foreign particles by phagocytes is initiated by the engagement of phagocytic receptors. We have previously reported that NimC1 is involved in the phagocytosis of bacteria in Drosophila melanogaster. We have identified a family of genes, the Nimrod gene superfamily, encoding characteristic NIM domain containing structural homologues of NimC1. In this work we studied the bacterium-binding properties of the Nimrod proteins by using a novel immunofluorescencebased flow cytometric assay. This method proved to be highly reproducible and suitable for investigations of the bacteriumbinding capacities of putative phagocytosis receptors. We found that NimC1, NimA, NimB1 and NimB2 bind bacteria significantly but differently. In this respect they are similar to other NIM domain containing receptors Eater and Draper.}, year = {2013}, eissn = {1644-3632}, pages = {633-645}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839; Galgóczi, László Norbert/0000-0002-6976-8910; Andó, István/0000-0002-4648-9396} } @article{MTMT:22865290, title = {A directed miniscreen for genes involved in the Drosophila anti-parasitoid immune response}, url = {https://m2.mtmt.hu/api/publication/22865290}, author = {Howell, L and Sampson, CJ and Xavier, MJ and Bolukbasi, E and Heck, MMS and Williams, MJ}, doi = {10.1007/s00251-011-0571-3}, journal-iso = {IMMUNOGENETICS}, journal = {IMMUNOGENETICS}, volume = {64}, unique-id = {22865290}, issn = {0093-7711}, year = {2012}, eissn = {1432-1211}, pages = {155-161} } @article{MTMT:1921048, title = {Cell lineage tracing reveals the plasticity of the hemocyte lineages and of the hematopoietic compartments in drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/1921048}, author = {Honti, Viktor and Csordás, Gábor and Márkus, Róbert and Kurucz, Judit Éva and Jankovics, Ferenc and Andó, István}, doi = {10.1016/j.molimm.2010.04.017}, journal-iso = {MOL IMMUNOL}, journal = {MOLECULAR IMMUNOLOGY}, volume = {47}, unique-id = {1921048}, issn = {0161-5890}, keywords = {Animals; Immunity, Innate; Immunity, Cellular; Receptors, Scavenger/genetics; Hemocytes/cytology/*physiology; *Hematopoiesis; Drosophila melanogaster/embryology/*immunology; Drosophila Proteins/genetics; *Cell Lineage}, year = {2010}, eissn = {1872-9142}, pages = {1997-2004}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839; Andó, István/0000-0002-4648-9396} }