@article{MTMT:34576476, title = {Gcm counteracts Toll-induced inflammation and impacts hemocyte number through cholinergic signaling}, url = {https://m2.mtmt.hu/api/publication/34576476}, author = {Bazzi, W. and Monticelli, S. and Delaporte, C. and Riet, C. and Giangrande, A. and Cattenoz, P.B.}, doi = {10.3389/fimmu.2023.1293766}, journal-iso = {FRONT IMMUNOL}, journal = {FRONTIERS IN IMMUNOLOGY}, volume = {14}, unique-id = {34576476}, issn = {1664-3224}, abstract = {Hemocytes, the myeloid-like immune cells of Drosophila, fulfill a variety of functions that are not completely understood, ranging from phagocytosis to transduction of inflammatory signals. We here show that downregulating the hemocyte-specific Glial cell deficient/Glial cell missing (Glide/Gcm) transcription factor enhances the inflammatory response to the constitutive activation of the Toll pathway. This correlates with lower levels of glutathione S-transferase, suggesting an implication of Glide/Gcm in reactive oxygen species (ROS) signaling and calling for a widespread anti-inflammatory potential of Glide/Gcm. In addition, our data reveal the expression of acetylcholine receptors in hemocytes and that Toll activation affects their expressions, disclosing a novel aspect of the inflammatory response mediated by neurotransmitters. Finally, we provide evidence for acetylcholine receptor nicotinic acetylcholine receptor alpha 6 (nAchRalpha6) regulating hemocyte proliferation in a cell autonomous fashion and for non-cell autonomous cholinergic signaling regulating the number of hemocytes. Altogether, this study provides new insights on the molecular pathways involved in the inflammatory response. Copyright © 2023 Bazzi, Monticelli, Delaporte, Riet, Giangrande and Cattenoz.}, keywords = {Animals; Inflammation; Inflammation; Inflammation; Inflammation; metabolism; PHENOTYPE; TRANSCRIPTION FACTOR; green fluorescent protein; CHROMATIN IMMUNOPRECIPITATION; DNA-BINDING PROTEINS; ARTICLE; TOLL; DROSOPHILA; DROSOPHILA; DROSOPHILA; HEMOCYTES; HEMOCYTES; animal; Cell Differentiation; Cell Differentiation; Genotype; reverse transcription polymerase chain reaction; nonhuman; cell proliferation; cholinergic nerve cell; Central Nervous System; Homeostasis; GLUTATHIONE TRANSFERASE; GENE ONTOLOGY; immunocompetent cell; blood cell; blood cell; reactive oxygen metabolite; DNA binding protein; upregulation; down regulation; neurotransmitter; cholinergic receptor stimulating agent; RNA extraction; cholinergic receptor; red fluorescent protein; glia cell; antibody labeling; choline acetyltransferase; cholinergic transmission; dopamine receptor; Drosophila Proteins; Hemolymph; embryo development; polypeptide antibiotic agent; Drosophila protein; hydroethidine; Cholinergic Agents; CRISPR-CAS9 system; RNA sequencing; gene expression level; melanotic neuroectodermal tumor of infancy; Glide/Gcm; nAchRalpha6}, year = {2023}, eissn = {1664-3224} } @article{MTMT:34576395, title = {The human leukemic oncogene MLL-AF4 promotes hyperplastic growth of hematopoietic tissues in Drosophila larvae}, url = {https://m2.mtmt.hu/api/publication/34576395}, author = {Johannessen, J.A. and Formica, M. and Haukeland, A.L.C. and Bråthen, N.R. and Al, Outa A. and Aarsund, M. and Therrien, M. and Enserink, J.M. and Knævelsrud, H.}, doi = {10.1016/j.isci.2023.107726}, journal-iso = {ISCIENCE}, journal = {ISCIENCE}, volume = {26}, unique-id = {34576395}, abstract = {MLL-rearranged (MLL-r) leukemias are among the leukemic subtypes with poorest survival, and treatment options have barely improved over the last decades. Despite increasing molecular understanding of the mechanisms behind these hematopoietic malignancies, this knowledge has had poor translation into the clinic. Here, we report a Drosophila melanogaster model system to explore the pathways affected in MLL-r leukemia. We show that expression of the human leukemic oncogene MLL-AF4 in the Drosophila hematopoietic system resulted in increased levels of circulating hemocytes and an enlargement of the larval hematopoietic organ, the lymph gland. Strikingly, depletion of Drosophila orthologs of known interactors of MLL-AF4, such as DOT1L, rescued the leukemic phenotype. In agreement, treatment with small-molecule inhibitors of DOT1L also prevented the MLL-AF4-induced leukemia-like phenotype. Taken together, this model provides an in vivo system to unravel the genetic interactors involved in leukemogenesis and offers a system for improved biological understanding of MLL-r leukemia. © 2023 The Author(s)}, keywords = {Oncology; Molecular Biology; CELL BIOLOGY}, year = {2023}, eissn = {2589-0042} } @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: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: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: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: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:32601830, title = {Characterization of the Drosophila Adult Hematopoietic System Reveals a Rare Cell Population With Differentiation and Proliferation Potential}, url = {https://m2.mtmt.hu/api/publication/32601830}, author = {Boulet, M. and Renaud, Y. and Lapraz, F. and Benmimoun, B. and Vandel, L. and Waltzer, L.}, doi = {10.3389/fcell.2021.739357}, journal-iso = {FRONT CELL DEV BIOL}, journal = {FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY}, volume = {9}, unique-id = {32601830}, issn = {2296-634X}, abstract = {While many studies have described Drosophila embryonic and larval blood cells, the hematopoietic system of the imago remains poorly characterized and conflicting data have been published concerning adult hematopoiesis. Using a combination of blood cell markers, we show that the adult hematopoietic system is essentially composed of a few distinct mature blood cell types. In addition, our transcriptomics results indicate that adult and larval blood cells have both common and specific features and it appears that adult hemocytes reactivate many genes expressed in embryonic blood cells. Interestingly, we identify a small set of blood cells that does not express differentiation markers but rather maintains the expression of the progenitor marker domeMeso. Yet, we show that these cells are derived from the posterior signaling center, a specialized population of cells present in the larval lymph gland, rather than from larval blood cell progenitors, and that their maintenance depends on the EBF transcription factor Collier. Furthermore, while these cells are normally quiescent, we find that some of them can differentiate and proliferate in response to bacterial infection. In sum, our results indicate that adult flies harbor a small population of specialized cells with limited hematopoietic potential and further support the idea that no substantial hematopoiesis takes place during adulthood. © Copyright © 2021 Boulet, Renaud, Lapraz, Benmimoun, Vandel and Waltzer.}, keywords = {DROSOPHILA; Hematopoiesis; imago; blood cell progenitor; Collier}, 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: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:32006305, title = {Phospho-Site Mutations in Transcription Factor Suppressor of Hairless Impact Notch Signaling Activity During Hematopoiesis in Drosophila}, url = {https://m2.mtmt.hu/api/publication/32006305}, author = {Frankenreiter, L. and Gahr, B.M. and Schmid, H. and Zimmermann, M. and Deichsel, S. and Hoffmeister, P. and Turkiewicz, A. and Borggrefe, T. and Oswald, F. and Nagel, A.C.}, doi = {10.3389/fcell.2021.658820}, journal-iso = {FRONT CELL DEV BIOL}, journal = {FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY}, volume = {9}, unique-id = {32006305}, issn = {2296-634X}, abstract = {The highly conserved Notch signaling pathway controls a multitude of developmental processes including hematopoiesis. Here, we provide evidence for a novel mechanism of tissue-specific Notch regulation involving phosphorylation of CSL transcription factors within the DNA-binding domain. Earlier we found that a phospho-mimetic mutation of the Drosophila CSL ortholog Suppressor of Hairless [Su(H)] at Ser269 impedes DNA-binding. By genome-engineering, we now introduced phospho-specific Su(H) mutants at the endogenous Su(H) locus, encoding either a phospho-deficient [Su(H)S269A] or a phospho-mimetic [Su(H)S269D] isoform. Su(H)S269D mutants were defective of Notch activity in all analyzed tissues, consistent with impaired DNA-binding. In contrast, the phospho-deficient Su(H)S269A mutant did not generally augment Notch activity, but rather specifically in several aspects of blood cell development. Unexpectedly, this process was independent of the corepressor Hairless acting otherwise as a general Notch antagonist in Drosophila. This finding is in agreement with a novel mode of Notch regulation by posttranslational modification of Su(H) in the context of hematopoiesis. Importantly, our studies of the mammalian CSL ortholog (RBPJ/CBF1) emphasize a potential conservation of this regulatory mechanism: phospho-mimetic RBPJS221D was dysfunctional in both the fly as well as two human cell culture models, whereas phospho-deficient RBPJS221A rather gained activity during fly hematopoiesis. Thus, dynamic phosphorylation of CSL-proteins within the DNA-binding domain provides a novel means to fine-tune Notch signal transduction in a context-dependent manner. © Copyright © 2021 Frankenreiter, Gahr, Schmid, Zimmermann, Deichsel, Hoffmeister, Turkiewicz, Borggrefe, Oswald and Nagel.}, keywords = {PHOSPHORYLATION; DROSOPHILA; Hematopoiesis; Notch signaling; Suppressor of Hairless}, 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:32601829, title = {Intact in situ Preparation of the Drosophila melanogaster Lymph Gland for a Comprehensive Analysis of Larval Hematopoiesis}, url = {https://m2.mtmt.hu/api/publication/32601829}, author = {Rodrigues, D. and VijayRaghavan, K. and Waltzer, L. and Inamdar, M.S.}, doi = {10.21769/BioProtoc.4204}, journal-iso = {BIO-PROTOCOL}, journal = {BIO-PROTOCOL}, volume = {11}, unique-id = {32601829}, issn = {2331-8325}, abstract = {[Abstract] Blood cells have a limited lifespan and are replenished by a small number of hematopoietic stem and progenitor cells (HSPCs). Adult vertebrate hematopoiesis occurs in the bone marrow, liver, and spleen, rendering a comprehensive analysis of the entire HSPC pool nearly impossible. The Drosophila blood system is well studied and has developmental, molecular, and functional parallels with that of vertebrates. Unlike vertebrates, post-embryonic hematopoiesis in Drosophila is essentially restricted to the larval lymph gland (LG), a multi-lobed organ that flanks the dorsal vessel. Because the anterior-most or primary lobes of the LG are easy to dissect out, their cellular and molecular characteristics have been studied in considerable detail. The 2-3 pairs of posterior lobes are more delicate and fragile and have largely been ignored. However, posterior lobes harbor a significant blood progenitor pool, and several hematopoietic mutants show differences in phenotype between the anterior and posterior lobes. Hence, a comprehensive analysis of the LG is important for a thorough understanding of Drosophila hematopoiesis. Most studies focus on isolating the primary lobes by methods that generally dislodge and damage other lobes. To obtain preparations of the whole LG, including intact posterior lobes, here we provide a detailed protocol for larval fillet dissection. This allows accessing and analyzing complete LG lobes, along with dorsal vessel and pericardial cells. We demonstrate that tissue architecture and integrity is maintained and provide methods for quantitative analysis. This protocol can be used to quickly and effectively isolate complete LGs from first instar larval to pupal stages and can be implemented with ease. © 2021 Bio-protocol LLC. All Rights Reserved.}, keywords = {DISSECTION; Drosophila hematopoiesis; Blood progenitor; Complete larval lymph gland; Posterior lobes; Secondary lobes; Tertiary lobes}, year = {2021} } @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: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: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:31686151, title = {Eater cooperates with Multiplexin to drive the formation of hematopoietic compartments}, url = {https://m2.mtmt.hu/api/publication/31686151}, author = {Csordás, Gábor and Grawe, Ferdinand and Uhlirova, Mirka}, doi = {10.7554/eLife.57297}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {9}, unique-id = {31686151}, issn = {2050-084X}, abstract = {Blood development in multicellular organisms relies on specific tissue microenvironments that nurture hematopoietic precursors and promote their self-renewal, proliferation, and differentiation. The mechanisms driving blood cell homing and their interactions with hematopoietic microenvironments remain poorly understood. Here, we use the Drosophila melanogaster model to reveal a pivotal role for basement membrane composition in the formation of hematopoietic compartments. We demonstrate that by modulating extracellular matrix components, the fly blood cells known as hemocytes can be relocated to tissue surfaces where they function similarly to their natural hematopoietic environment. We establish that the Collagen XV/XVIII ortholog Multiplexin in the tissue-basement membranes and the phagocytosis receptor Eater on the hemocytes physically interact and are necessary and sufficient to induce immune cell-tissue association. These results highlight the cooperation of Multiplexin and Eater as an integral part of a homing mechanism that specifies and maintains hematopoietic sites in Drosophila}, year = {2020}, eissn = {2050-084X}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839} } @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:33777424, title = {Constitutive activation of cellular immunity underlies the evolution of resistance to infection in drosophila}, url = {https://m2.mtmt.hu/api/publication/33777424}, author = {Leitão, A.B. and Arunkumar, R. and Day, J.P. and Geldman, E.M. and Morin-Poulard, I. and Crozatier, M. and Jiggins, F.M.}, doi = {10.7554/ELIFE.59095}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {9}, unique-id = {33777424}, issn = {2050-084X}, abstract = {Organisms rely on inducible and constitutive immune defences to combat infection. Constitutive immunity enables a rapid response to infection but may carry a cost for uninfected individuals, leading to the prediction that it will be favoured when infection rates are high. When we exposed populations of Drosophila melanogaster to intense parasitism by the parasitoid wasp Leptopilina boulardi, they evolved resistance by developing a more reactive cellular immune response. Using single-cell RNA sequencing, we found that immune-inducible genes had become constitutively upregulated. This was the result of resistant larvae differentiating precursors of specialized immune cells called lamellocytes that were previously only produced after infection. Therefore, populations evolved resistance by genetically hard-wiring the first steps of an induced immune response to become constitutive. © 2020, eLife Sciences Publications Ltd. All rights reserved.}, keywords = {Animals; Female; Female; Male; Male; GENETICS; ARTICLE; EVOLUTION; DROSOPHILA; HEMOCYTES; immunology; animal; gene expression regulation; gene expression regulation; nonhuman; larva; larva; Infections; parasitology; Drosophila melanogaster; Drosophila melanogaster; DISEASE RESISTANCE; DISEASE RESISTANCE; human cell; immunocompetent cell; cellular immunity; cellular immunity; immune response; blood cell; Immunity, Cellular; Biological Evolution; Wasps; WASP; single cell RNA seq}, year = {2020}, eissn = {2050-084X}, pages = {1-24} } @article{MTMT:31469409, title = {The Posterior Signaling Center Is an Important Microenvironment for Homeostasis of the Drosophila Lymph Gland}, url = {https://m2.mtmt.hu/api/publication/31469409}, author = {Luo, Fangzhou and Yu, Shichao and Jin, Li Hua}, doi = {10.3389/fcell.2020.00382}, journal-iso = {FRONT CELL DEV BIOL}, journal = {FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY}, volume = {8}, unique-id = {31469409}, issn = {2296-634X}, abstract = {Hematopoiesis is a necessary process for development and immune defense in Drosophila from the embryonic period to adulthood. There are two main stages in this process: the first stage occurs in the head mesoderm during the embryonic stage, and the second occurs in a specialized hematopoietic organ along the dorsal vessel, the lymph gland, during the larval stage. The lymph gland consists of paired lobes, each of which has distinct regions: the cortical zone (CZ), which contains mature hemocytes; the medullary zone (MZ), which contains hematopoietic progenitors; and the posterior signaling center (PSC), which specifically expresses the early B-cell factor (EBF) transcription factor Collier (Col) and the HOX factor Antennapedia (Antp) to form a microenvironment similar to that of the mammalian bone marrow hematopoietic stem cell niche. The PSC plays a key role in regulating hematopoietic progenitor differentiation. Moreover, the PSC contributes to the cellular immune response to wasp parasitism triggered by elevated ROS levels. Two recent studies have revealed that hematopoietic progenitor maintenance is directly regulated by Col expressed in the MZ and is independent of the PSC, challenging the traditional model. In this review, we summarize the regulatory networks of PSC cell proliferation, the controversy regarding PSC-mediated regulation of hematopoietic progenitor differentiation, and the wasp egg infection response. In addition, we discuss why the PSC is an ideal model for investigating mammalian hematopoietic stem cell niches and leukemia.}, keywords = {DIFFERENTIATION; LEUKEMIA; DROSOPHILA; immune response; Signaling network; lymph gland; posterior signaling center; hematopoietic stem cells niche}, year = {2020}, eissn = {2296-634X} } @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:31686969, title = {Endocrine regulation of immunity in insects}, url = {https://m2.mtmt.hu/api/publication/31686969}, author = {Nunes, Catarina and Sucena, Elio and Koyama, Takashi}, doi = {10.1111/febs.15581}, journal-iso = {FEBS J}, journal = {FEBS JOURNAL}, unique-id = {31686969}, issn = {1742-464X}, abstract = {Organisms have constant contact with potentially harmful agents that can compromise their fitness. However, most of the times these agents fail to cause serious disease by virtue of the rapid and efficient immune responses elicited in the host that can range from behavioural adaptations to immune system triggering. The immune system of insects does not comprise the adaptive arm, making it less complex than that of vertebrates, but key aspects of the activation and regulation of innate immunity are conserved across different phyla. This is the case for the hormonal regulation of immunity as a part of the broad organismal responses to external conditions under different internal states. In insects, depending on the physiological circumstances, distinct hormones either enhance or suppress the immune response integrating individual (and often collective) responses physiologically and behaviourally. In this review, we provide an overview of our current knowledge on the endocrine regulation of immunity in insects, its mechanisms and implications on metabolic adaptation and behaviour. We highlight the importance of this multilayered regulation of immunity in survival and reproduction (fitness) and its dependence on the hormonal integration with other mechanisms and life-history traits.}, keywords = {metabolism; INSECT; HORMONES; Immunity; ANTIMICROBIAL PEPTIDES; ecdysone; Juvenile hormone; IIS (insulin signalling); Imd signalling; Toll signalling}, year = {2020}, eissn = {1742-4658}, orcid-numbers = {Sucena, Elio/0000-0001-8810-870X; Koyama, Takashi/0000-0003-4203-114X} } @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: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: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: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: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} } @inbook{MTMT:31568110, title = {Drosophila melanogaster and its nephrocytes: A versatile model for glomerular research}, url = {https://m2.mtmt.hu/api/publication/31568110}, author = {Odenthal, Johanna and Brinkkoetter, Paul Thomas}, booktitle = {Methods in Kidney Cell Biology - Part B}, doi = {10.1016/bs.mcb.2019.03.011}, unique-id = {31568110}, abstract = {Glomerular disorders are a predominant cause of chronic kidney diseases and end-stage renal failure. Especially podocytes, epithelial cells which represent the outermost part of the filtration barrier, are affected by disease and experience a gradual loss of function. Despite recent advances in identifying potential pathways underlying podocyte injury, treatment remains challenging. It is therefore desirable to employ suitable model organisms in order to study glomerular disease and elucidate affected pathways. Due to its diverse ways of genetic manipulation and high genomic conservation, Drosophila melanogaster is a powerful model organism for biomedical research. The fly was recently used to assess podocytopathies by exploiting the nephrocyte system. Nephrocytes are spherical cells within the body cavity of the fly responsible for detoxification and clearance of unwanted substances. More importantly, they share many characteristics with mammalian podocytes. Here, we summarize how to use Drosophila as a model organism for podocyte research. We discuss examples of techniques that can be used to genetically manipulate nephrocytes and provide protocols for nephrocyte isolation and for morphological as well as functional analysis.}, year = {2019}, pages = {217-+} } @article{MTMT:30907595, title = {Simu-dependent clearance of dying cells regulates macrophage function and inflammation resolution}, url = {https://m2.mtmt.hu/api/publication/30907595}, author = {Roddie, Hannah Grace and Armitage, Emma Louise and Coates, Jonathon Alexis and Johnston, Simon Andrew and Evans, Iwan Robert}, doi = {10.1371/journal.pbio.2006741}, journal-iso = {PLOS BIOL}, journal = {PLOS BIOLOGY}, volume = {17}, unique-id = {30907595}, issn = {1544-9173}, abstract = {Macrophages encounter and clear apoptotic cells during normal development and homeostasis, including at numerous sites of pathology. Clearance of apoptotic cells has been intensively studied, but the effects of macrophage-apoptotic cell interactions on macrophage behaviour are poorly understood. Using Drosophila embryos, we have exploited the ease of manipulating cell death and apoptotic cell clearance in this model to identify that the loss of the apoptotic cell clearance receptor Six-microns-under (Simu) leads to perturbation of macrophage migration and inflammatory responses via pathological levels of apoptotic cells. Removal of apoptosis ameliorates these phenotypes, while acute induction of apoptosis phenocopies these defects and reveals that phagocytosis of apoptotic cells is not necessary for their anti-inflammatory action. Furthermore, Simu is necessary for clearance of necrotic debris and retention of macrophages at wounds. Thus, Simu is a general detector of damaged self and represents a novel molecular player regulating macrophages during resolution of inflammation.}, year = {2019}, eissn = {1545-7885} } @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:30510582, title = {Hedgehog signaling from the Posterior Signaling Center maintains U-shaped expression and a prohemocyte population in Drosophila}, url = {https://m2.mtmt.hu/api/publication/30510582}, author = {Baldeosingh, Rajkumar and Gao, Hongjuan and Wu, Xiaorong and Fossett, Nancy}, doi = {10.1016/j.ydbio.2018.06.020}, journal-iso = {DEV BIOL}, journal = {DEVELOPMENTAL BIOLOGY}, volume = {441}, unique-id = {30510582}, issn = {0012-1606}, abstract = {Hematopoietic progenitor choice between multipotency and differentiation is tightly regulated by intrinsic factors and extrinsic signals from the surrounding microenvironment. The Drosophila melanogaster hematopoietic lymph gland has emerged as a powerful tool to investigate mechanisms that regulate hematopoietic progenitor choice in vivo. The lymph gland contains progenitor cells, which share key characteristics with mammalian hematopoietic progenitors such as quiescence, multipotency and niche dependence. The lymph gland is zonally arranged, with progenitors located in medullary zone, differentiating cells in the cortical zone, and the stem cell niche or Posterior Signaling Center (PSC) residing at the base of the medullary zone (MZ). This arrangement facilitates investigations into how signaling from the microenvironment controls progenitor choice. The Drosophila Friend of GATA transcriptional regulator, U-shaped, is a conserved hematopoietic regulator. To identify additional novel intrinsic and extrinsic regulators that interface with U-shaped to control hematopoiesis, we conducted an in vivo screen for factors that genetically interact with u-shaped. Smoothened, a downstream effector of Hedgehog signaling, was one of the factors identified in the screen. Here we report our studies that characterized the relationship between Smoothened and U-shaped. We showed that the PSC and Hedgehog signaling are required for U-shaped expression and that U-shaped is an important intrinsic progenitor regulator. These observations identify a potential link between the progenitor regulatory machinery and extrinsic signals from the PSC. Furthermore, we showed that both Hedgehog signaling and the PSC are required to maintain a subpopulation of progenitors. This led to a delineation of PSC-dependent versus PSC-independent progenitors and provided further evidence that the MZ progenitor population is heterogeneous. Overall, we have identified a connection between a conserved hematopoietic master regulator and a putative stem cell niche, which adds to our understanding of how signals from the microenvironment regulate progenitor multipotency.}, year = {2018}, eissn = {1095-564X}, pages = {132-145} } @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:26891561, title = {A Genetic Screen Reveals an Unexpected Role for Yorkie Signaling in JAK/STAT-Dependent Hematopoietic Malignancies in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/26891561}, author = {Anderson, Abigail M and Bailetti, Alessandro A and Rodkin, Elizabeth and De, Atish and Bach, Erika A}, doi = {10.1534/g3.117.044172}, journal-iso = {G3-GENES GENOM GENET}, journal = {G3-GENES GENOMES GENETICS}, volume = {7}, unique-id = {26891561}, issn = {2160-1836}, year = {2017}, eissn = {2160-1836}, pages = {2427-2438} } @article{MTMT:3249679, title = {Genes encoding cuticular proteins are components of the Nimrod gene cluster in Drosophila.}, url = {https://m2.mtmt.hu/api/publication/3249679}, author = {Cinege, Gyöngyi Ilona and Zsámboki, János and Vidal-Quadras, M and Uv, A and Csordás, Gábor and Honti, Viktor and Gábor, Erika and Hegedűs, Zoltán and Varga, Gergely István and Kovács, Attila Lajos and Juhász, Gábor and Williams, MJ and Andó, István and Kurucz, Judit Éva}, doi = {10.1016/j.ibmb.2017.06.006}, journal-iso = {INSECT BIOCHEM MOLEC}, journal = {INSECT BIOCHEMISTRY AND MOLECULAR BIOLOGY}, volume = {87}, unique-id = {3249679}, issn = {0965-1748}, abstract = {The Nimrod gene cluster, located on the second chromosome of Drosophila melanogaster, is the largest synthenic unit of the Drosophila genome. Nimrod genes show blood cell specific expression and code for phagocytosis receptors that play a major role in fruit fly innate immune functions. We previously identified three homologous genes (vajk-1, vajk-2 and vajk-3) located within the Nimrod cluster, which are unrelated to the Nimrod genes, but are homologous to a fourth gene (vajk-4) located outside the cluster. Here we show that, unlike the Nimrod candidates, the Vajk proteins are expressed in cuticular structures of the late embryo and the late pupa, indicating that they contribute to cuticular barrier functions.}, year = {2017}, eissn = {1879-0240}, pages = {45-54}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839; Varga, Gergely István/0000-0001-9073-5788; Juhász, Gábor/0000-0001-8548-8874; Andó, István/0000-0002-4648-9396} } @article{MTMT:27055182, title = {dOCRL maintains immune cell quiescence by regulating endosomal traffic}, url = {https://m2.mtmt.hu/api/publication/27055182}, author = {Del Signore, Steven J and Biber, Sarah A and Lehmann, Katherine S and Heimler, Stephanie R and Rosenfeld, Benjamin H and Eskin, Tania L and Sweeney, Sean T and Rodal, Avital A}, doi = {10.1371/journal.pgen.1007052}, journal-iso = {PLOS GENET}, journal = {PLOS GENETICS}, volume = {13}, unique-id = {27055182}, issn = {1553-7390}, year = {2017}, eissn = {1553-7404} } @{MTMT:34589227, title = {Advances in myeloid-like cell origins and functions in the model organism Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/34589227}, author = {El, Chamy L. and Matt, N. and Reichhart, J.-M.}, booktitle = {Myeloid Cells in Health and Disease}, doi = {10.1128/9781555819194.ch5}, unique-id = {34589227}, abstract = {Innate immunity shields all metazoans against infections. Its main features, including sensing, signaling, and effector mechanisms, are conserved from invertebrates to vertebrates. The hallmark of innate immunity is its reliance on a limited set of non-clonally-distributed receptors, which detect signature molecules of microbial origin and activate subsequent effector mechanisms. This concept, coined by Charles Janeway in 1989 as the self-versus-microbial-nonself discrimination system, has opened a large field of research for the so-called pattern recognition receptors (PRRs) and their cognate microbial elicitors, the pathogen-associated molecular patterns (1). Drosophila has rapidly emerged as a particularly suitable model organism for this research. Indeed, like all invertebrates, Drosophila exclusively relies on an innate immune system, which fends off infections in highly contaminated environments. Most importantly, Drosophila has benefited from more than a century of laboratory-use experience, yielding a wide array of molecular and genetic tools. Investigations on the defense reactions in flies rapidly provided valuable insights into the evolutionary conservation between insects and mammals, including humans, of the signal transduction pathways that control the innate immune system (2). Most prominent is the seminal finding in 1996 of the chief role of the Toll signaling pathway in the control of fungal infections in Drosophila (3). This study paved the way for the identification of the first mammalian PRR, Toll-like receptor 4 (the launching member of the TLR family), and the understanding of the innate immune system’s molecular mechanisms for sensing, signaling, and activation of adaptive immunity (4 - 6). Following more than 2 decades of in-depth analysis exploiting several infection models combined with genetic and genomic approaches, research on the Drosophila immune system revealed complex interconnected humoral and cellular processes, both of which show striking similarities with those of mammals. In this review, we provide a global view of the Drosophila host defense while drawing particular attention to the role of its monocyte-macrophage-like cells, the plasmatocytes. We provide general insights on the recent advances in Drosophila hematopoiesis and give a comprehensive summary on the so-far identified receptors involved in microbial detection, binding, and the ensuing internalization processes. © 2017 American Society for Microbiology, Washington, DC.}, keywords = {PHAGOCYTOSIS; Drosophila melanogaster; Antimicrobial peptide; Drosophila hematopoiesis; Diaminopimelic acid-type peptidoglycan; Drosophila plasmatocyte; Phagocytic receptor}, year = {2017}, pages = {59-77} } @{MTMT:32006335, title = {Advances in myeloid-like cell origins and functions in the model organism Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/32006335}, author = {El, Chamy L. and Matt, N. and Reichhart, J.-M.}, booktitle = {Myeloid Cells in Health and Disease}, doi = {10.1128/9781555819194.ch5}, unique-id = {32006335}, abstract = {Innate immunity shields all metazoans against infections. Its main features, including sensing, signaling, and effector mechanisms, are conserved from invertebrates to vertebrates. The hallmark of innate immunity is its reliance on a limited set of non-clonally-distributed receptors, which detect signature molecules of microbial origin and activate subsequent effector mechanisms. This concept, coined by Charles Janeway in 1989 as the self-versus-microbial-nonself discrimination system, has opened a large field of research for the so-called pattern recognition receptors (PRRs) and their cognate microbial elicitors, the pathogen-associated molecular patterns (1). Drosophila has rapidly emerged as a particularly suitable model organism for this research. Indeed, like all invertebrates, Drosophila exclusively relies on an innate immune system, which fends off infections in highly contaminated environments. Most importantly, Drosophila has benefited from more than a century of laboratory-use experience, yielding a wide array of molecular and genetic tools. Investigations on the defense reactions in flies rapidly provided valuable insights into the evolutionary conservation between insects and mammals, including humans, of the signal transduction pathways that control the innate immune system (2). Most prominent is the seminal finding in 1996 of the chief role of the Toll signaling pathway in the control of fungal infections in Drosophila (3). This study paved the way for the identification of the first mammalian PRR, Toll-like receptor 4 (the launching member of the TLR family), and the understanding of the innate immune system’s molecular mechanisms for sensing, signaling, and activation of adaptive immunity (4 - 6). Following more than 2 decades of in-depth analysis exploiting several infection models combined with genetic and genomic approaches, research on the Drosophila immune system revealed complex interconnected humoral and cellular processes, both of which show striking similarities with those of mammals. In this review, we provide a global view of the Drosophila host defense while drawing particular attention to the role of its monocyte-macrophage-like cells, the plasmatocytes. We provide general insights on the recent advances in Drosophila hematopoiesis and give a comprehensive summary on the so-far identified receptors involved in microbial detection, binding, and the ensuing internalization processes. © 2017 American Society for Microbiology, Washington, DC.}, keywords = {PHAGOCYTOSIS; Drosophila melanogaster; Antimicrobial peptide; Drosophila hematopoiesis; Diaminopimelic acid-type peptidoglycan; Drosophila plasmatocyte; Phagocytic receptor}, year = {2017}, pages = {59-77} } @article{MTMT:26536389, title = {Advances in Myeloid-Like Cell Origins and Functions in the Model Organism Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/26536389}, author = {El, Chamy Laure and Matt, Nicolas and Reichhart, Jean-Marc}, doi = {10.1128/microbiolspec.MCHD-0038-2016}, journal-iso = {MICROBIOL SPEC}, journal = {MICROBIOLOGY SPECTRUM}, volume = {5}, unique-id = {26536389}, issn = {2165-0497}, year = {2017}, eissn = {2165-0497} } @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:26536387, title = {Screening and Analysis of Janelia FlyLight Project Enhancer-Gal4 Strains Identifies Multiple Gene Enhancers Active During Hematopoiesis in Normal and Wasp-Challenged Drosophila Larvae}, url = {https://m2.mtmt.hu/api/publication/26536387}, author = {Tokusumi, Tsuyoshi and Tokusumi, Yumiko and Brahier, Mark S and Lam, Victoria and Stoller-Conrad, Jessica R and Kroeger, Paul T and Schulz, Robert A}, doi = {10.1534/g3.116.034439}, journal-iso = {G3-GENES GENOM GENET}, journal = {G3-GENES GENOMES GENETICS}, volume = {7}, unique-id = {26536387}, issn = {2160-1836}, year = {2017}, eissn = {2160-1836}, pages = {437-448} } @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:25771414, title = {Anopheles gambiae hemocytes exhibit transient states of activation}, url = {https://m2.mtmt.hu/api/publication/25771414}, author = {Bryant, William B and Michel, Kristin}, doi = {10.1016/j.dci.2015.10.020}, journal-iso = {DEV COMP IMMUNOL}, journal = {DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY}, volume = {55}, unique-id = {25771414}, issn = {0145-305X}, year = {2016}, eissn = {1879-0089}, pages = {119-129} } @article{MTMT:26377269, title = {Dpp dependent Hematopoietic stem cells give rise to Hh dependent blood progenitors in larval lymph gland of Drosophila}, url = {https://m2.mtmt.hu/api/publication/26377269}, author = {Dey, Nidhi Sharma and Ramesh, Parvathy and Chugh, Mayank and Mandal, Sudip and Mandal, Lolitika}, doi = {10.7554/eLife.18295}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {5}, unique-id = {26377269}, issn = {2050-084X}, year = {2016}, eissn = {2050-084X} } @article{MTMT:26203751, title = {Development of the Cellular Immune System of Drosophila Requires the Membrane Attack Complex/Perforin-Like Protein Torso-Like}, url = {https://m2.mtmt.hu/api/publication/26203751}, author = {Forbes-Beadle, Lauren and Crossman, Tova and Johnson, Travis K and Burke, Richard and Warr, Coral G and Whisstock, James C}, doi = {10.1534/genetics.115.185462}, journal-iso = {GENETICS}, journal = {GENETICS}, volume = {204}, unique-id = {26203751}, issn = {0016-6731}, year = {2016}, eissn = {1943-2631}, pages = {675-U1161} } @article{MTMT:25771630, title = {Insect immunology and hematopoiesis}, url = {https://m2.mtmt.hu/api/publication/25771630}, author = {Hillyer, Julian F}, doi = {10.1016/j.dci.2015.12.006}, journal-iso = {DEV COMP IMMUNOL}, journal = {DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY}, volume = {58}, unique-id = {25771630}, issn = {0145-305X}, year = {2016}, eissn = {1879-0089}, pages = {102-118} } @article{MTMT:26377268, title = {Drosophila hematopoiesis under normal conditions and in response to immune stress}, url = {https://m2.mtmt.hu/api/publication/26377268}, author = {Letourneau, Manon and Lapraz, Francois and Sharma, Anurag and Vanzo, Nathalie and Waltzer, Lucas and Crozatier, Michele}, doi = {10.1002/1873-3468.12327}, journal-iso = {FEBS LETT}, journal = {FEBS LETTERS}, volume = {590}, unique-id = {26377268}, issn = {0014-5793}, year = {2016}, eissn = {1873-3468}, pages = {4034-4051} } @article{MTMT:26237558, title = {Genetic Screen in Drosophila Larvae Links ird1 Function to Toll Signaling in the Fat Body and Hemocyte Motility}, url = {https://m2.mtmt.hu/api/publication/26237558}, author = {Schmid, Martin R and Anderl, Ines and Vo, Hoa T M and Valanne, Susanna and Yang, Hairu and Kronhamn, Jesper and Ramet, Mika and Rusten, Tor Erik and Hultmark, Dan}, doi = {10.1371/journal.pone.0159473}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {11}, unique-id = {26237558}, issn = {1932-6203}, year = {2016}, eissn = {1932-6203}, orcid-numbers = {Yang, Hairu/0000-0002-9420-878X} } @{MTMT:26674055, title = {Hematopoiesis and hemocytes in pancrustacean and molluscan models}, url = {https://m2.mtmt.hu/api/publication/26674055}, author = {Smith, VJ and Accorsi, A and Malagoli, D}, booktitle = {The Evolution of the Immune System: Conservation and Diversification}, doi = {10.1016/B978-0-12-801975-7.00001-3}, publisher = {Elsevier Inc.}, unique-id = {26674055}, year = {2016}, pages = {1-28} } @article{MTMT:24796091, title = {New ways to make a blood cell}, url = {https://m2.mtmt.hu/api/publication/24796091}, author = {Anderl, Ines and Hultmark, Dan}, doi = {10.7554/eLife.06877}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {4}, unique-id = {24796091}, issn = {2050-084X}, year = {2015}, eissn = {2050-084X} } @article{MTMT:2853633, title = {The Nimrod transmembrane receptor Eater is required for hemocyte attachment to the sessile compartment in Drosophila melanogaster.}, url = {https://m2.mtmt.hu/api/publication/2853633}, author = {Bretscher, AJ and Honti, Viktor and Binggeli, O and Burri, O and Poidevin, M and Kurucz, Judit Éva and Zsámboki, János and Andó, István and Lemaitre, B}, doi = {10.1242/bio.201410595}, journal-iso = {BIOL OPEN}, journal = {BIOLOGY OPEN}, volume = {4}, unique-id = {2853633}, issn = {2046-6390}, abstract = {Eater is an EGF-like repeat transmembrane receptor of the Nimrod family and is expressed in Drosophila hemocytes. Eater was initially identified for its role in phagocytosis of both Gram-positive and Gram-negative bacteria. We have deleted eater and show that it appears to be required for efficient phagocytosis of Gram-positive but not Gram-negative bacteria. However, the most striking phenotype of eater deficient larvae is the near absence of sessile hemocytes, both plasmatocyte and crystal cell types. The eater deletion is the first loss of function mutation identified that causes absence of the sessile hemocyte state. Our study shows that Eater is required cell-autonomously in plasmatocytes for sessility. However, the presence of crystal cells in the sessile compartment requires Eater in plasmatocytes. We also show that eater deficient hemocytes exhibit a cell adhesion defect. Collectively, our data uncovers a new requirement of Eater in enabling hemocyte attachment at the sessile compartment and points to a possible role of Nimrod family members in hemocyte adhesion.}, year = {2015}, eissn = {2046-6390}, pages = {355-363}, orcid-numbers = {Andó, István/0000-0002-4648-9396} } @article{MTMT:24982068, title = {Active Hematopoietic Hubs in Drosophila Adults Generate Hemocytes and Contribute to Immune Response}, url = {https://m2.mtmt.hu/api/publication/24982068}, author = {Ghosh, S and Singh, A and Mandal, S and Mandal, L}, doi = {10.1016/j.devcel.2015.03.014}, journal-iso = {DEV CELL}, journal = {DEVELOPMENTAL CELL}, volume = {33}, unique-id = {24982068}, issn = {1534-5807}, year = {2015}, eissn = {1878-1551}, pages = {478-488} } @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:24797542, title = {Drosophila sessile hemocyte clusters are true hematopoietic tissues that regulate larval blood cell differentiation}, url = {https://m2.mtmt.hu/api/publication/24797542}, author = {Leitao, Alexandre B and Sucena, Elio}, doi = {10.7554/eLife.06166}, journal-iso = {ELIFE}, journal = {ELIFE}, volume = {4}, unique-id = {24797542}, issn = {2050-084X}, abstract = {Virtually all species of coelomate animals contain blood cells that display a division of labor necessary for homeostasis. This functional partition depends upon the balance between proliferation and differentiation mostly accomplished in the hematopoietic organs. In Drosophila melanogaster, the lymph gland produces plasmatocytes and crystal cells that are not released until pupariation. Yet, throughout larval development, both hemocyte types increase in numbers. Mature plasmatocytes can proliferate but it is not known if crystal cell numbers increase by self-renewal or by de novo differentiation. We show that new crystal cells in third instar larvae originate through a Notch-dependent process of plasmatocyte transdifferentiation. This process occurs in the sessile clusters and is contingent upon the integrity of these structures. The existence of this hematopoietic tissue, relying on structure-dependent signaling events to promote blood homeostasis, creates a new paradigm for addressing outstanding questions in Drosophila hematopoiesis and establishing further parallels with vertebrate systems. © 2015, eLife Sciences Publications Ltd. All rights reserved.}, year = {2015}, eissn = {2050-084X}, pages = {1-38} } @article{MTMT:2853634, title = {Multinucleated Giant Hemocytes Are Effector Cells in Cell-Mediated Immune Responses of Drosophila}, url = {https://m2.mtmt.hu/api/publication/2853634}, author = {Márkus, Róbert and Lerner, Zita and Honti, Viktor and Csordás, Gábor and Zsámboki, János and Cinege, Gyöngyi Ilona and Párducz, Árpád and Lukacsovich, Tamás and Kurucz, Judit Éva and Andó, István}, doi = {10.1159/000369618}, journal-iso = {J INNATE IMMUN}, journal = {JOURNAL OF INNATE IMMUNITY}, volume = {7}, unique-id = {2853634}, issn = {1662-811X}, abstract = {We identified and characterized a so far unrecognized cell type, dubbed the multinucleated giant hemocyte (MGH), in the ananassae subgroup of Drosophilidae. Here, we describe the functional and ultrastructural characteristics of this novel blood cell type as well as its characterization with a set of discriminative immunological markers. MGHs are encapsulating cells that isolate and kill the parasite without melanization. They share some properties with but differ considerably from lamellocytes, the encapsulating cells of Drosophila melanogaster, the broadly used model organism in studies of innate immunity. MGHs are nonproliferative effector cells that are derived from phagocytic cells of the sessile tissue and the circulation, but do not exhibit phagocytic activity. In contrast to lamellocytes, MGHs are gigantic cells with filamentous projections and contain many nuclei, which are the result of the fusion of several cells. Although the structure of lamellocytes and MGHs differ remarkably, their function in the elimination of parasites is similar, which is potentially the result of the convergent evolution of interactions between hosts and parasites in different geographic regions. MGHs are highly motile and share several features with mammalian multinucleated giant cells, a syncytium of macrophages formed during granulomatous inflammation. © 2015 S. Karger AG, Basel}, year = {2015}, eissn = {1662-8128}, pages = {340-353}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839; Andó, István/0000-0002-4648-9396} } @article{MTMT:24796089, title = {The Black cells phenotype is caused by a point mutation in the Drosophila pro-phenoloxidase 1 gene that triggers melanization and hematopoietic defects}, url = {https://m2.mtmt.hu/api/publication/24796089}, author = {Neyen, Claudine and Binggeli, Olivier and Roversi, Pietro and Bertin, Lise and Sleiman, Maroun Bou and Lemaitre, Bruno}, doi = {10.1016/j.dci.2014.12.011}, journal-iso = {DEV COMP IMMUNOL}, journal = {DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY}, volume = {50}, unique-id = {24796089}, issn = {0145-305X}, year = {2015}, eissn = {1879-0089}, pages = {166-174} } @article{MTMT:25771415, title = {Drosophila Rabex-5 restricts Notch activity in hematopoietic cells and maintains hematopoietic homeostasis}, url = {https://m2.mtmt.hu/api/publication/25771415}, author = {Reimels, Theresa A and Pfleger, Cathie M}, doi = {10.1242/jcs.174433}, journal-iso = {J CELL SCI}, journal = {JOURNAL OF CELL SCIENCE}, volume = {128}, unique-id = {25771415}, issn = {0021-9533}, year = {2015}, eissn = {1477-9137}, pages = {4512-4525} } @article{MTMT:24975884, title = {Edin Expression in the Fat Body Is Required in the Defense Against Parasitic Wasps in Drosophila melanogaster}, url = {https://m2.mtmt.hu/api/publication/24975884}, author = {Vanha-aho, LM and Anderl, I and Vesala, L and Hultmark, D and Valanne, S and Ramet, M}, doi = {10.1371/journal.ppat.1004895}, journal-iso = {PLOS PATHOG}, journal = {PLOS PATHOGENS}, volume = {11}, unique-id = {24975884}, issn = {1553-7366}, year = {2015}, eissn = {1553-7374} } @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:24356904, title = {Differences in Cellular Immune Competence Explain Parasitoid Resistance for Two Coleopteran Species}, url = {https://m2.mtmt.hu/api/publication/24356904}, author = {Fors, L and Markus, R and Theopold, U and Hamback, PA}, doi = {10.1371/journal.pone.0108795}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {9}, unique-id = {24356904}, issn = {1932-6203}, year = {2014}, eissn = {1932-6203} } @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:24399545, title = {JAK/STAT Pathway in Drosophila Immunity}, url = {https://m2.mtmt.hu/api/publication/24399545}, author = {Myllymaki, H and Ramet, M}, doi = {10.1111/sji.12170}, journal-iso = {SCAND J IMMUNOL}, journal = {SCANDINAVIAN JOURNAL OF IMMUNOLOGY}, volume = {79}, unique-id = {24399545}, issn = {0300-9475}, year = {2014}, eissn = {1365-3083}, pages = {377-385} } @article{MTMT:24874773, title = {Control of Drosophila Blood Cell Activation via Toll Signaling in the Fat Body}, url = {https://m2.mtmt.hu/api/publication/24874773}, author = {Schmid, Martin R and Anderl, Ines and Vesala, Laura and Vanha-aho, Leena-Maija and Deng, Xiao-Juan and Ramet, Mika and Hultmark, Dan}, doi = {10.1371/journal.pone.0102568}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {9}, unique-id = {24874773}, issn = {1932-6203}, year = {2014}, eissn = {1932-6203} } @article{MTMT:32913596, title = {An unexpected link between notch signaling and ROS in restricting the differentiation of hematopoietic progenitors in Drosophila}, url = {https://m2.mtmt.hu/api/publication/32913596}, author = {Small, C. and Ramroop, J. and Otazo, M. and Huang, L.H. and Saleque, S. and Govind, S.}, doi = {10.1534/genetics.113.159210}, journal-iso = {GENETICS}, journal = {GENETICS}, volume = {197}, unique-id = {32913596}, issn = {0016-6731}, abstract = {A fundamental question in hematopoietic development is how multipotent progenitors achieve precise identities, while the progenitors themselves maintain quiescence. In Drosophila melanogaster larvae, multipotent hematopoietic progenitors support the production of three lineages, exhibit quiescence in response to cues from a niche, and from their differentiated progeny. Infection by parasitic wasps alters the course of hematopoiesis. Here we address the role of Notch (N) signaling in lamellocyte differentiation in response to wasp infection. We show that Notch activity is moderately high and ubiquitous in all cells of the lymph gland lobes, with crystal cells exhibiting the highest levels. Wasp infection reduces Notch activity, which results in fewer crystal cells and more lamellocytes. Robust lamellocyte differentiation is induced even in N mutants. Using RNA interference knockdown of N, Serrate, and neuralized (neur), and twin clone analysis of a N null allele, we show that all three genes inhibit lamellocyte differentiation. However, unlike its cell-autonomous function in crystal cell development, Notch's inhibitory influence on lamellocyte differentiation is not cell autonomous. High levels of reactive oxygen species in the lymph gland lobes, but not in the niche, accompany NRNAi-induced lamellocyte differentiation and lobe dispersal. Our results define a novel dual role for Notch signaling in maintaining competence for basal hematopoiesis: while crystal cell development is encouraged, lamellocytic fate remains repressed. Repression of Notch signaling in fly hematopoiesis is important for host defense against natural parasitic wasp infections. These findings can serve as a model to understand how reactive oxygen species and Notch signals are integrated and interpreted in vivo. © 2014 by the Genetics Society of America.}, keywords = {Animals; Female; Female; Male; Male; metabolism; GENETICS; immunohistochemistry; CALCIUM-BINDING PROTEINS; ARTICLE; signal transduction; signal transduction; signal transduction; signal peptide; animal; Cell Differentiation; Cell Differentiation; Membrane Proteins; membrane protein; priority journal; controlled study; Cytology; nonhuman; animal tissue; animal experiment; parasitology; RNA Interference; RNA Interference; Drosophila melanogaster; Drosophila melanogaster; protein expression; Reactive oxygen species; reactive oxygen metabolite; reactive oxygen metabolite; cell maturation; hematopoietic stem cell; Receptors, Notch; Intercellular Signaling Peptides and Proteins; lymph node; Hematopoiesis; Hematopoiesis; Hematopoiesis; calcium binding protein; Hematopoietic Stem Cells; hypoxia inducible factor 1alpha; Ubiquitin-Protein Ligases; gene activity; ubiquitin protein ligase; Notch receptor; Notch receptor; Drosophila Proteins; Wasps; Drosophila protein; WASP; null allele; Serrate proteins; neur protein, Drosophila; notch protein, Drosophila}, year = {2014}, eissn = {1943-2631}, pages = {471-483} } @article{MTMT:23238862, title = {Signal transduction pathways, intrinsic regulators, and the control of cell fate choice}, url = {https://m2.mtmt.hu/api/publication/23238862}, author = {Fossett, N}, doi = {10.1016/j.bbagen.2012.06.005}, journal-iso = {BBA-GEN SUBJECTS}, journal = {BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS}, volume = {1830}, unique-id = {23238862}, issn = {0304-4165}, year = {2013}, eissn = {1872-8006}, pages = {2375-2384} } @article{MTMT:25022905, title = {Drosophila E-Cadherin Functions in Hematopoietic Progenitors to Maintain Multipotency and Block Differentiation}, url = {https://m2.mtmt.hu/api/publication/25022905}, author = {Gao, Hongjuan and Wu, Xiaorong and Fossett, Nancy}, doi = {10.1371/journal.pone.0074684}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {8}, unique-id = {25022905}, issn = {1932-6203}, year = {2013}, eissn = {1932-6203} } @article{MTMT:2372552, title = {Variation of NimC1 expression in Drosophila stocks and transgenic strains.}, url = {https://m2.mtmt.hu/api/publication/2372552}, author = {Honti, Viktor and Cinege, Gyöngyi Ilona and Csordás, Gábor and Kurucz, Judit Éva and Zsámboki, János and Evans, CJ and Banerjee, U and Andó, István}, doi = {10.4161/fly.25654}, journal-iso = {FLY}, journal = {FLY}, volume = {7}, unique-id = {2372552}, issn = {1933-6934}, abstract = {The NimC1 molecule has been described as a phagocytosis receptor, and is being used as a marker for professional phagocytes, the plasmatocytes, in Drosophila melanogaster. In studies including tumor-biology, developmental biology, and cell mediated immunity, monoclonal antibodies (P1a and P1b) to the NimC1 antigen are used. As we observed that these antibodies did not react with plasmatocytes of several strains and genetic combinations, a molecular analysis was performed on the structure of the nimC1 gene. We found 2 deletions and an insertion within the nimC1 gene, which may result in the production of a truncated NimC1 protein. The NimC1 positivity was regained by recombining the mutation with a wild-type allele or by using nimC1 mutant lines under heterozygous conditions. By means of these procedures or gaining access to the recombined stock, NimC1 can be used as a marker for phagocytic cells in the majority of the possible genetic backgrounds.}, year = {2013}, eissn = {1933-6942}, pages = {263-266}, orcid-numbers = {Csordás, Gábor/0000-0001-6871-6839; Andó, István/0000-0002-4648-9396} } @article{MTMT:23238861, title = {Spatial and temporal in vivo analysis of circulating and sessile immune cells in mosquitoes: hemocyte mitosis following infection}, url = {https://m2.mtmt.hu/api/publication/23238861}, author = {King, JG and Hillyer, JF}, doi = {10.1186/1741-7007-11-55}, journal-iso = {BMC BIOL}, journal = {BMC BIOLOGY}, volume = {11}, unique-id = {23238861}, issn = {1741-7007}, year = {2013}, eissn = {1741-7007} } @{MTMT:23469621, title = {The Evolutionary Origins and Presence of Eosinophils in Extant Species}, url = {https://m2.mtmt.hu/api/publication/23469621}, author = {McGarry, MP}, booktitle = {Eosinophils in Health and Disease}, doi = {10.1016/B978-0-12-394385-9.00002-X}, publisher = {Elsevier Inc.}, unique-id = {23469621}, year = {2013}, pages = {13-18} } @article{MTMT:21893824, title = {Structural and functional characterization of pseudopodocyte, a shaggy immune cell produced by two Drosophila species of the obscura group}, url = {https://m2.mtmt.hu/api/publication/21893824}, author = {Havard, S and Doury, G and Ravallec, M and Brehélin, M and Prévost, G and Eslin, P}, doi = {10.1016/j.dci.2011.05.009}, journal-iso = {DEV COMP IMMUNOL}, journal = {DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY}, volume = {36}, unique-id = {21893824}, issn = {0145-305X}, year = {2012}, eissn = {1879-0089}, pages = {323-331} } @article{MTMT:22865289, title = {High Hemocyte Load Is Associated with Increased Resistance against Parasitoids in Drosophila suzukii, a Relative of D. melanogaster}, url = {https://m2.mtmt.hu/api/publication/22865289}, author = {Kacsoh, BZ and Schlenke, TA}, doi = {10.1371/journal.pone.0034721}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {7}, unique-id = {22865289}, issn = {1932-6203}, year = {2012}, eissn = {1932-6203} } @article{MTMT:22865270, title = {Adaptive Evolution of a Novel Drosophila Lectin Induced by Parasitic Wasp Attack}, url = {https://m2.mtmt.hu/api/publication/22865270}, author = {Keebaugh, ES and Schlenke, TA}, doi = {10.1093/molbev/msr191}, journal-iso = {MOL BIOL EVOL}, journal = {MOLECULAR BIOLOGY AND EVOLUTION}, volume = {29}, unique-id = {22865270}, issn = {0737-4038}, year = {2012}, eissn = {1537-1719}, pages = {565-577} } @article{MTMT:22865283, title = {The RhoGEF Zizimin-related acts in the Drosophila cellular immune response via the Rho GTPases Rac2 and Cdc42}, url = {https://m2.mtmt.hu/api/publication/22865283}, author = {Sampson, CJ and Valanne, S and Fauvarque, MO and Hultmark, D and Ramet, M and Williams, MJ}, doi = {10.1016/j.dci.2012.05.004}, journal-iso = {DEV COMP IMMUNOL}, journal = {DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY}, volume = {38}, unique-id = {22865283}, issn = {0145-305X}, year = {2012}, eissn = {1879-0089}, pages = {160-168} } @article{MTMT:22865258, title = {The Drosophila larva as a tool to study gut-associated macrophages: PI3K regulates a discrete hemocyte population at the proventriculus}, url = {https://m2.mtmt.hu/api/publication/22865258}, author = {Zaidman-Remy, A and Regan, JC and Brandao, AS and Jacinto, A}, doi = {10.1016/j.dci.2011.10.013}, journal-iso = {DEV COMP IMMUNOL}, journal = {DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY}, volume = {36}, unique-id = {22865258}, issn = {0145-305X}, year = {2012}, eissn = {1879-0089}, pages = {638-647} } @article{MTMT:22226818, title = {Drosophila: a model for studying genetic and molecular aspects of haematopoiesis and associated leukaemias}, url = {https://m2.mtmt.hu/api/publication/22226818}, author = {Crozatier, M and Vincent, A}, doi = {10.1242/dmm.007351}, journal-iso = {DIS MODEL MECH}, journal = {DISEASE MODELS & MECHANISMS}, volume = {4}, unique-id = {22226818}, issn = {1754-8403}, year = {2011}, eissn = {1754-8411}, pages = {439-445} } @article{MTMT:25811016, title = {Drosophila immunity research on the move}, url = {https://m2.mtmt.hu/api/publication/25811016}, author = {Eleftherianos, I and Schneider, D}, doi = {10.4161/fly.5.3.17028}, journal-iso = {FLY}, journal = {FLY}, volume = {5}, unique-id = {25811016}, issn = {1933-6934}, year = {2011}, eissn = {1933-6942}, pages = {247-254} } @article{MTMT:22226819, title = {Drosophila cellular immunity: a story of migration and adhesion}, url = {https://m2.mtmt.hu/api/publication/22226819}, author = {Fauvarque, MO and Williams, MJ}, doi = {10.1242/jcs.064592}, journal-iso = {J CELL SCI}, journal = {JOURNAL OF CELL SCIENCE}, volume = {124}, unique-id = {22226819}, issn = {0021-9533}, year = {2011}, eissn = {1477-9137}, pages = {1373-1382} } @article{MTMT:22209209, title = {Odd-Skipped Maintains Prohemocyte Potency and Blocks Blood Cell Development in Drosophila}, url = {https://m2.mtmt.hu/api/publication/22209209}, author = {Gao, HJ and Wu, XR and Fossett, N}, doi = {10.1002/dvg.20711}, journal-iso = {GENESIS}, journal = {GENESIS: THE JOURNAL OF GENETICS AND DEVELOPMENT}, volume = {49}, unique-id = {22209209}, issn = {1526-954X}, year = {2011}, eissn = {1526-968X}, pages = {105-116} } @article{MTMT:22296153, title = {Germ line differentiation factor Bag of Marbles is a regulator of hematopoietic progenitor maintenance during Drosophila hematopoiesis}, url = {https://m2.mtmt.hu/api/publication/22296153}, author = {Tokusumi, T and Tokusumi, Y and Hopkins, DW and Shoue, DA and Corona, L and Schulz, RA}, doi = {10.1242/dev.069336}, journal-iso = {DEVELOPMENT}, journal = {DEVELOPMENT}, volume = {138}, unique-id = {22296153}, issn = {0950-1991}, year = {2011}, eissn = {1477-9129}, pages = {3879-3884} } @article{MTMT:22209208, title = {The protein P23 identifies capsule-forming plasmatocytes in the moth Pseudoplusia includens}, url = {https://m2.mtmt.hu/api/publication/22209208}, author = {Zhang, S and Clark, KD and Strand, MR}, doi = {10.1016/j.dci.2010.12.006}, journal-iso = {DEV COMP IMMUNOL}, journal = {DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY}, volume = {35}, unique-id = {22209208}, issn = {0145-305X}, year = {2011}, eissn = {1879-0089}, pages = {501-510} } @article{MTMT:22226823, title = {Hematopoietic progenitors and hemocyte lineages in the Drosophila lymph gland}, url = {https://m2.mtmt.hu/api/publication/22226823}, author = {Krzemien, J and Oyallon, J and Crozatier, M and Vincent, A}, doi = {10.1016/j.ydbio.2010.08.003}, journal-iso = {DEV BIOL}, journal = {DEVELOPMENTAL BIOLOGY}, volume = {346}, unique-id = {22226823}, issn = {0012-1606}, year = {2010}, eissn = {1095-564X}, pages = {310-319} } @article{MTMT:22841687, title = {Cellular immunity and pathogen strategies in combative interactions involving Drosophila hosts and their endoparasitic wasps}, url = {https://m2.mtmt.hu/api/publication/22841687}, author = {Nappi, AJ}, journal-iso = {INV SURVIVAL J (ISJ)}, journal = {INVERTEBRATE SURVIVAL JOURNAL}, volume = {7}, unique-id = {22841687}, issn = {1824-307X}, year = {2010}, eissn = {1824-307X}, pages = {198-210} } @article{MTMT:22226822, title = {Lineage Tracing of Lamellocytes Demonstrates Drosophila Macrophage Plasticity}, url = {https://m2.mtmt.hu/api/publication/22226822}, author = {Stofanko, M and Kwon, SY and Badenhorst, P}, doi = {10.1371/journal.pone.0014051}, journal-iso = {PLOS ONE}, journal = {PLOS ONE}, volume = {5}, unique-id = {22226822}, issn = {1932-6203}, year = {2010}, eissn = {1932-6203} } @article{MTMT:22296154, title = {Serpent, Suppressor of Hairless and U-shaped are crucial regulators of hedgehog niche expression and prohemocyte maintenance during Drosophila larval hematopoiesis}, url = {https://m2.mtmt.hu/api/publication/22296154}, author = {Tokusumi, Y and Tokusumi, T and Stoller-Conrad, J and Schulz, RA}, doi = {10.1242/dev.053728}, journal-iso = {DEVELOPMENT}, journal = {DEVELOPMENT}, volume = {137}, unique-id = {22296154}, issn = {0950-1991}, year = {2010}, eissn = {1477-9129}, pages = {3561-3568} }