Réponses antivirales chez le moustique Aedes

@article{nehmar_therapeutic_2017,

title = {Therapeutic Modulation of Plasmacytoid Dendritic Cells in Experimental Arthritis},

author = {Ramzi Nehmar and Ghada Alsaleh and Benjamin Voisin and Vincent Flacher and Alexandre Mariotte and Victoria Saferding and Antonia Puchner and Birgit Niederreiter and Thierry Vandamme and Gernot Schabbauer and Philippe Kastner and Susan Chan and Peggy Kirstetter and Martin Holcmann and Christopher Mueller and Jean Sibilia and Seiamak Bahram and Stephan Blüml and Philippe Georgel},

doi = {10.1002/art.40225},

issn = {2326-5205},

year  = {2017},

date = {2017-01-01},

journal = {Arthritis & Rheumatology (Hoboken, N.J.)},

volume = {69},

number = {11},

pages = {2124--2135},

abstract = {OBJECTIVE: The role of plasmacytoid dendritic cells (PDCs) and type I interferons (IFNs) in rheumatoid arthritis (RA) remains a subject of controversy. This study was undertaken to explore the contribution of PDCs and type I IFNs to RA pathogenesis using various animal models of PDC depletion and to monitor the effect of localized PDC recruitment and activation on joint inflammation and bone damage. 

METHODS: Mice with K/BxN serum-induced arthritis, collagen-induced arthritis, and human tumor necrosis factor transgene insertion were studied. Symptoms were evaluated by visual scoring, quantification of paw swelling, determination of cytokine levels by enzyme-linked immunosorbent assay, and histologic analysis. Imiquimod-dependent therapeutic effects were monitored by transcriptome analysis (using quantitative reverse transcriptase-polymerase chain reaction) and flow cytometric analysis of the periarticular tissue. 

RESULTS: PDC-deficient mice showed exacerbation of inflammatory and arthritis symptoms after arthritogenic serum transfer. In contrast, enhancing PDC recruitment and activation to arthritic joints by topical application of the Toll-like receptor 7 (TLR-7) agonist imiquimod significantly ameliorated arthritis in various mouse models. Imiquimod induced an IFN signature and led to reduced infiltration of inflammatory cells. 

CONCLUSION: The therapeutic effects of imiquimod on joint inflammation and bone destruction are dependent on TLR-7 sensing by PDCs and type I IFN signaling. Our findings indicate that local recruitment and activation of PDCs represents an attractive therapeutic opportunity for RA patients.},

keywords = {Activation, Adjuvants, Aminoquinolines, Analysis, Animal, Animals, arthritis, Assay, cancer, Cells, cytokine, Cytokines, Dendritic Cells, DEPLETION, Disease Models, drug effects, Enzyme-Linked Immunosorbent Assay, Experimental, Flow Cytometry, Gene Expression Profiling, Genetics, GLYCOPROTEIN, Glycoproteins, Human, Humans, IFN, IKAROS, Ikaros Transcription Factor, imiquimod, Immunologic, Immunology, immunopathology, inflammation, interferon, Interferon Type I, interferons, Knockout, Membrane, Membrane Glycoproteins, METHOD, methods, Mice, MODULATION, mouse, Necrosis, NECROSIS-FACTOR-ALPHA, pathogenesis, Patients, Pharmacology, physiology, plasmacytoid dendritic cells, Protein, Receptor, Reverse Transcriptase Polymerase Chain Reaction, rheumatoid, rheumatoid arthritis, Serum, signaling, Team-Mueller, TLR7, Toll-Like Receptor 7, TOPICAL APPLICATION, Transcription, TRANSCRIPTION FACTOR, transcriptome, transgenic, tumor, Tumor Necrosis Factor, Tumor Necrosis Factor-alpha},

pubstate = {published},

tppubtype = {article}

}

@article{baron_parental_2013,

title = {Parental transfer of the antimicrobial protein LBP/BPI protects Biomphalaria glabrata eggs against oomycete infections},

author = {Olga Lucia Baron and Pieter van West and Benoit Industri and Michel Ponchet and Géraldine Dubreuil and Benjamin Gourbal and Jean-Marc Reichhart and Christine Coustau},

doi = {10.1371/journal.ppat.1003792},

issn = {1553-7374},

year  = {2013},

date = {2013-01-01},

journal = {PLoS Pathog.},

volume = {9},

number = {12},

pages = {e1003792},

abstract = {Vertebrate females transfer antibodies via the placenta, colostrum and milk or via the egg yolk to protect their immunologically immature offspring against pathogens. This evolutionarily important transfer of immunity is poorly documented in invertebrates and basic questions remain regarding the nature and extent of parental protection of offspring. In this study, we show that a lipopolysaccharide binding protein/bactericidal permeability increasing protein family member from the invertebrate Biomphalaria glabrata (BgLBP/BPI1) is massively loaded into the eggs of this freshwater snail. Native and recombinant proteins displayed conserved LPS-binding, antibacterial and membrane permeabilizing activities. A broad screening of various pathogens revealed a previously unknown biocidal activity of the protein against pathogenic water molds (oomycetes), which is conserved in human BPI. RNAi-dependent silencing of LBP/BPI in the parent snails resulted in a significant reduction of reproductive success and extensive death of eggs through oomycete infections. This work provides the first functional evidence that a LBP/BPI is involved in the parental immune protection of invertebrate offspring and reveals a novel and conserved biocidal activity for LBP/BPI family members.},

keywords = {Acute-Phase Proteins, Animals, Antimicrobial Cationic Peptides, Biomphalaria, Blood Proteins, Carrier Proteins, Cell Membrane, Cell Membrane Permeability, Cloning, Escherichia coli, Female, Immunity, infection, M3i, Maternally-Acquired, Membrane Glycoproteins, Microbial Sensitivity Tests, Molecular, Oomycetes, Recombinant Proteins, reichhart, Zygote},

pubstate = {published},

tppubtype = {article}

}

@article{marmey_cd14_2006,

title = {CD14 and CD169 expression in human lymph nodes and spleen: specific expansion of CD14+C},

author = {B Marmey and C Boix and J B Barbaroux and M C Dieu-Nosjean and J Diebold and J Audouin and W H Fridman and C G Mueller and T J Molina},

year  = {2006},

date = {2006-01-01},

journal = {Hum.Pathol.},

volume = {37},

number = {0046-8177 (Print)},

pages = {68--77},

abstract = {The mononuclear phagocyte system of human lymphoid tissue comprises macrophages and dendritic cells (DCs). The heterogeneity of the non-DC mononuclear phagocyte population in human lymphoid tissue has been little addressed. Here, we studied the expression of 2 monocyte-derived markers, CD14 and CD169 (sialoadhesin), in reactive human lymphoid tissue as well as in a series of 51 B-cell lymphomas by immunohistochemistry on paraffin-embedded tissue. We confirmed that lymph node sinusoidal monocyte-derived cells were the only population staining for CD169. Although most sinusoidal histiocytes also expressed CD14, monocyte-derived cells with phagocytosis such as erythrophagocytosis, anthracosis, or tingible bodies macrophage lacked CD14 and CD169. Among B-cell lymphomas, splenic marginal zone lymphoma was the only one associated with an expansion of the CD14(+)CD169(+) cells in the cords. With respect to nodal B-cell lymphomas, CD14(+) cells were rare among B-chronic lymphocytic leukemia, follicular lymphoma (FL), mantle cell lymphoma (MCL). However, strikingly, we found a strong expansion of CD14(+)CD169(-) cells in numerous diffuse large B-cell lymphomas (DLBCLs), except in cases associated with numerous mitoses, apoptotic bodies, and tingible bodies macrophages. When cultivated in granulocyte/macrophage colony stimulating factor/interleukin 4, DLBCL purified CD14(+) cells differentiate into plasmacytoid cells, expressing DC-specific intercellular adhesion molecule 3-grabbing nonintegrin, suggesting dendritic cell differentiation potential. Our observation fits well with the lymph node and host response cluster signatures described in the gene profiling signatures of DLBCL. However, the role of this CD14(+) population that may constitute a microenvironment-related marker of this subgroup of DLBCL remains to be determined},

keywords = {Adhesion, Antigen, Antigens, B-Cell, Biological, CD14, Cell Differentiation, CELL SEPARATION, Dendritic Cells, Differentiation, Diffuse, Direct, Expression, Flow Cytometry, Fluorescent Antibody Technique, Gene, GLYCOPROTEIN, Glycoproteins, granulocyte/macrophage-colony, Human, Humans, Immunoenzyme Techniques, Immunohistochemistry, Immunologic, Large B-Cell, leukemia, LYMPH, LYMPH NODE, Lymph Nodes, Lymphadenitis, Lymphoid Tissue, LYMPHOMA, Macrophage, Macrophages, Membrane, Membrane Glycoproteins, metabolism, Monocytes, pathology, Phagocytosis, Receptor, Receptors, SIALOADHESIN, SPLEEN, Team-Mueller, tumor, Tumor Markers},

pubstate = {published},

tppubtype = {article}

}

@article{barbaroux_tumor_2006,

title = {Tumor necrosis factor-alpha- and IL-4-independent development of Langerhans cell-like dendritic cells from M-CSF-conditioned precursors},

author = {Jean-Baptiste Barbaroux and Wing-Hong Kwan and Jean-Pierre Allam and Natalija Novak and Thomas Bieber and Wolf H Fridman and Richard Groves and Chris G Mueller},

doi = {10.1038/sj.jid.5700023},

issn = {0022-202X},

year  = {2006},

date = {2006-01-01},

journal = {The Journal of Investigative Dermatology},

volume = {126},

number = {1},

pages = {114--120},

abstract = {GM-CSF and transforming growth factor beta (TGFbeta ) are required for the generation of Langerhans cells (LC), members of the dendritic cell (DC) family. Tumor necrosis factor alpha (TNFalpha) and IL-4 can enhance LC differentiation from human monocytes or CD34(+) progenitors. Here, we show that M-CSF-cultured DC precursors derived from CD34(+) progenitors resemble dermal CD14(+) cells and readily convert to LC-like DC in GM-CSF/TGFbeta. The cells express Langerin, CD1a, and CCR6, migrate in response to CCR6 ligand CCL20, and contain Birbeck granules. TNFalpha and IL-4, added separately or together, have an inhibitory effect on LC differentiation. Cells differentiated in the presence of IL-4 and TNFalpha express low levels of CCR7. This suggests that M-CSF-conditioned DC precursors retain the capacity to efficiently undergo a differentiation program, giving rise to LC-like DC solely through the effect of GM-CSF and TGFbeta.},

keywords = {Antigens, C-Type, Carrier Proteins, CC, CCR6, CD, CD1, CD34, Cell Differentiation, Chemokine, Chemokine CCL20, chemokines, Cytokines, DERMIS, FRANZ, Granulocyte-Macrophage Colony-Stimulating Factor, Hematopoietic Stem Cells, Humans, IL-4, Interleukin-4, Langerhans Cells, Lectins, Lipopolysaccharide Receptors, M-CSF, Macrophage Colony-Stimulating Factor, Macrophage Inflammatory Proteins, Mannose-Binding Lectins, Membrane Glycoproteins, murine, RANK ligand, Receptor Activator of Nuclear Factor-kappa B, Receptors, Surface, Team-Mueller, TNF ALPHA, Tumor Necrosis Factor-alpha},

pubstate = {published},

tppubtype = {article}

}

@article{martinelli_evolution_2005,

title = {Evolution and integration of innate immune systems from fruit flies to man: lessons and questions},

author = {Cosimo Martinelli and Jean-Marc Reichhart},

doi = {10.1179/096805105X37411},

issn = {0968-0519},

year  = {2005},

date = {2005-01-01},

journal = {J. Endotoxin Res.},

volume = {11},

number = {4},

pages = {243--248},

abstract = {Despite broad differences in morphology, ecology and behavior, the fruit fly Drosophila melanogaster and humans show a remarkably high degree of conservation for many molecular, cellular, and developmental aspects of their biology. During the last decade, similarities have also been discovered in some of the mechanisms regulating their innate immune system. These parallels regard mainly the Toll-like receptor family and the intracellular signaling pathways involved in the control of the immune response. However, if the overall similarities are important, the detailed pathogen recognition mechanisms differ significantly between fly and humans, highlighting a complicated evolutionary history of the metazoan innate defenses. In this review, we will discuss the main similarities and differences between the two types of organisms. We hope that this current knowledge will be used as a starting point for a more comprehensive view of innate immunity within the broad variety of metazoan phyla.},

keywords = {Animals, Biological Evolution, Cell Surface, Forecasting, Humans, Immunity, Immunological, Innate, M3i, Membrane Glycoproteins, Models, Receptors, reichhart, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors},

pubstate = {published},

tppubtype = {article}

}

@article{weber_ligand-receptor_2005,

title = {Ligand-receptor and receptor-receptor interactions act in concert to activate signaling in the Drosophila toll pathway},

author = {Alexander N R Weber and Martin C Moncrieffe and Monique Gangloff and Jean-Luc Imler and Nicholas J Gay},

doi = {10.1074/jbc.M502074200},

issn = {0021-9258},

year  = {2005},

date = {2005-01-01},

journal = {The Journal of Biological Chemistry},

volume = {280},

number = {24},

pages = {22793--22799},

abstract = {In Drosophila, the signaling pathway mediated by the Toll receptor is critical for the establishment of embryonic dorso-ventral pattern and for innate immune responses to bacterial and fungal pathogens. Toll is activated by high affinity binding of the cytokine Spätzle, a dimeric ligand of the cystine knot family. In vertebrates, a related family of Toll-like receptors play a critical role in innate immune responses. Despite the importance of this family of receptors, little is known about the biochemical events that lead to receptor activation and signaling. Here, we show that Spätzle binds to the N-terminal region of Toll and, using biophysical methods, that the binding is complex. The two binding events that cause formation of the cross-linked complex are non-equivalent: the first Toll ectodomain binds Spätzle with an affinity 3-fold higher than the second molecule suggesting that pathway activation involves negative cooperativity. We further show that the Toll ectodomains are able to form low affinity dimers in solution and that juxtamembrane sequences of Toll are critical for the activation or derepression of the pathway. These results, taken together, suggest a mechanism of signal transduction that requires both ligand-receptor and receptor-receptor interactions.},

keywords = {Amino Acid, Animals, Biophysical Phenomena, Biophysics, Body Patterning, Calorimetry, Cell Line, Cell Surface, Cross-Linking Reagents, Cytokines, dimerization, Electrophoresis, Humans, imler, ligands, Luciferases, M3i, Membrane Glycoproteins, Polyacrylamide Gel, Protein Binding, Protein Structure, Receptors, Recombinant Proteins, Sequence Homology, Signal Transduction, Tertiary, Time Factors, Toll-Like Receptors, Ultracentrifugation},

pubstate = {published},

tppubtype = {article}

}

@article{imler_biology_2004,

title = {Biology of Toll receptors: lessons from insects and mammals},

author = {Jean-Luc Imler and Liangbiao Zheng},

doi = {10.1189/jlb.0403160},

issn = {0741-5400},

year  = {2004},

date = {2004-01-01},

journal = {Journal of Leukocyte Biology},

volume = {75},

number = {1},

pages = {18--26},

abstract = {Toll receptors are type I transmembrane proteins that play important roles in development and immunity in animals. Comparison of the genomes of mouse and human on one side and of the fruitfly Drosophila and the mosquito Anopheles (two dipteran insects) on the other, revealed that the four species possess a similar number of Toll receptors (approximately 10). However, phylogenetic analyses indicate that the families of Toll receptors expanded independently in insects and mammals. We review recent results on these receptors, which point to differences in the activation and signaling between Tolls in insects and Toll-like receptors (TLRs) in mammals. Whereas mammalian TLRs appear to be solely dedicated to host-defense, insect Tolls may be predominantly linked to other functions, probably developmental.},

keywords = {Animals, Anopheles, Cell Surface, Humans, imler, M3i, Membrane Glycoproteins, Mice, Phylogeny, Plant Physiological Phenomena, Receptors, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors},

pubstate = {published},

tppubtype = {article}

}

@article{imler_toll-dependent_2004,

title = {Toll-dependent and Toll-independent immune responses in Drosophila},

author = {Jean-Luc Imler and Dominique Ferrandon and Julien Royet and Jean-Marc Reichhart and Charles Hetru and Jules A Hoffmann},

doi = {10.1179/096805104225005887},

issn = {0968-0519},

year  = {2004},

date = {2004-01-01},

journal = {Journal of Endotoxin Research},

volume = {10},

number = {4},

pages = {241--246},

abstract = {The multifaceted response of the fruitfly Drosophila melanogaster to infection by a wide range of microbes is complex and remarkably efficient. Its most prominent aspect is the immune-inducible expression of a set of potent antimicrobial peptides. Genetic analysis of the regulation of the genes encoding these peptides has led to the identification of the receptor Toll as an essential component of the fly's host defense system. In addition, these studies have revealed that the response to Gram-negative bacterial infections involves Toll-independent mechanisms, and that the sensing of infection involves two structurally distinct sets of molecules--the PGRPs and the GNBPs/betaGRPs.},

keywords = {Acute-Phase Proteins, Animals, Blood Proteins, Cell Surface, ferrandon, hoffmann, imler, Insect Proteins, M3i, Membrane Glycoproteins, Receptors, reichhart, Toll-Like Receptor 5, Toll-Like Receptors, Up-Regulation},

pubstate = {published},

tppubtype = {article}

}

@article{reichhart_tlr5_2003,

title = {TLR5 takes aim at bacterial propeller},

author = {Jean-Marc Reichhart},

doi = {10.1038/ni1203-1159},

issn = {1529-2908},

year  = {2003},

date = {2003-12-01},

journal = {Nat. Immunol.},

volume = {4},

number = {12},

pages = {1159--1160},

keywords = {Animals, Bacterial Physiological Phenomena, Cell Surface, Flagella, Flagellin, Humans, M3i, Membrane Glycoproteins, Receptors, reichhart, Toll-Like Receptor 5, Toll-Like Receptors},

pubstate = {published},

tppubtype = {article}

}

@article{hoffmann_immune_2003,

title = {The immune response of Drosophila},

author = {Jules A Hoffmann},

doi = {10.1038/nature02021},

issn = {1476-4687},

year  = {2003},

date = {2003-11-01},

journal = {Nature},

volume = {426},

number = {6962},

pages = {33--38},

abstract = {Drosophila mounts a potent host defence when challenged by various microorganisms. Analysis of this defence by molecular genetics has now provided a global picture of the mechanisms by which this insect senses infection, discriminates between various classes of microorganisms and induces the production of effector molecules, among which antimicrobial peptides are prominent. An unexpected result of these studies was the discovery that most of the genes involved in the Drosophila host defence are homologous or very similar to genes implicated in mammalian innate immune defences. Recent progress in research on Drosophila immune defence provides evidence for similarities and differences between Drosophila immune responses and mammalian innate immunity.},

keywords = {Animals, Cell Surface, hoffmann, Immunity, Innate, M3i, Membrane Glycoproteins, Receptors, Signal Transduction, Toll-Like Receptor 5, Toll-Like Receptors},

pubstate = {published},

tppubtype = {article}

}

@article{bilak_toll_2003,

title = {Toll and Toll-like receptors in Drosophila},

author = {Hana Bilak and S Tauszig-Delamasure and Jean-Luc Imler},

doi = {10.1042/},

issn = {0300-5127},

year  = {2003},

date = {2003-06-01},

journal = {Biochemical Society Transactions},

volume = {31},

number = {Pt 3},

pages = {648--651},

abstract = {The Drosophila Toll receptor controls the immune response to Gram-positive bacteria and fungi by activating a signalling pathway partially conserved throughout evolution. The Drosophila genome encodes eight additional Toll-related receptors, most of which appear to carry out developmental rather than immune functions. One exception may be Toll-9, which shares structural and functional similarities with mammalian TLRs.},

keywords = {Animals, Biological Evolution, Cell Surface, Fungi, Genome, Gram-Negative Bacteria, Gram-Positive Bacteria, imler, M3i, Membrane Glycoproteins, Receptors, Toll-Like Receptor 5, Toll-Like Receptors},

pubstate = {published},

tppubtype = {article}

}

@article{imler_toll_2003,

title = {Toll signaling: the TIReless quest for specificity},

author = {Jean-Luc Imler and Jules A Hoffmann},

doi = {10.1038/ni0203-105},

issn = {1529-2908},

year  = {2003},

date = {2003-02-01},

journal = {Nature Immunology},

volume = {4},

number = {2},

pages = {105--106},

keywords = {Animals, Cell Surface, Dendritic Cells, hoffmann, Humans, imler, Immunological, Interferon-beta, M3i, Membrane Glycoproteins, Mice, Models, Protein Structure, Receptors, Signal Transduction, Tertiary, Toll-Like Receptors},

pubstate = {published},

tppubtype = {article}

}

@article{bates_adamdec1_2002,

title = {The ADAMDEC1 (decysin) gene structure: evolution by duplication in a metalloprotease gene cluster on chromosome 8p12},

author = {Elizabeth E M Bates and Wolf H Fridman and Chris G F Mueller},

doi = {10.1007/s00251-002-0430-3},

issn = {0093-7711},

year  = {2002},

date = {2002-05-01},

journal = {Immunogenetics},

volume = {54},

number = {2},

pages = {96--105},

abstract = {Members of the ADAM superfamily of metalloprotease genes are involved in a number of biological processes, including fertilization, neurogenesis, muscle development, and the immune response. These proteins have been classified into several groups. The prototypic ADAM family is comprised of a pro-domain, a metalloprotease domain, a disintegrin domain, a cysteine-rich region, a transmembrane domain, and a variable cytoplasmic tail. We recently identified a novel member of this superfamily, ADAMDEC1 (decysin). Due to the partial lack of a disintegrin domain and the total lack of a cysteine-rich domain, this protein has been placed in a novel subclass of the ADAM gene family. We have investigated the gene structure of the human and mouse ADAMDEC1 and have revealed a metalloprotease gene cluster on human Chromosome 8p12 comprising ADAMDEC1, ADAM7, and ADAM28. Our results suggest that ADAMDEC1 has arisen by partial gene duplication from an ancestral gene at this locus and has acquired a novel function. ADAMDEC1 is expressed in the immune system, by dendritic cells and macrophages. The relatedness of ADAMDEC1, ADAM7, and ADAM28 suggests that these proteases share a similar function.},

keywords = {ADAM Proteins, Amino Acid Sequence, Animals, Base Sequence, Chromosomes, Evolution, Gene Dosage, Gene Duplication, Genetic, Human, Humans, Inbred BALB C, Macaca mulatta, Membrane Glycoproteins, Metalloendopeptidases, Mice, Molecular, Molecular Sequence Data, Multigene Family, Pair 8, Promoter Regions, Sequence Alignment, Team-Mueller},

pubstate = {published},

tppubtype = {article}

}

@article{hoffmann_drosophila_2002,

title = {Drosophila innate immunity: an evolutionary perspective},

author = {Jules A Hoffmann and Jean-Marc Reichhart},

doi = {10.1038/ni0202-121},

issn = {1529-2908},

year  = {2002},

date = {2002-02-01},

journal = {Nat. Immunol.},

volume = {3},

number = {2},

pages = {121--126},

abstract = {In response to microbial infections, Drosophila mounts a multifaceted immune response involving humoral reactions that culminate in the destruction of invading organisms by lytic peptides. These defense mechanisms are activated via two distinct signaling pathways. One of these, the Toll pathway, controls resistance to fungal and Gram-positive bacterial infections, whereas the Imd pathway is responsible for defense against Gram-negative bacterial infections. Current evidence indicates that recognition of infectious nonself agents results from interactions between microbial wall components and extracellular pattern recognition proteins. We discuss here evolutionary perspectives on our present understanding of the antimicrobial defenses of Drosophila.},

keywords = {Animals, Biological Evolution, Cell Surface, hoffmann, Immunity, Immunological, Innate, M3i, Membrane Glycoproteins, Models, Receptors, reichhart, Signal Transduction, Toll-Like Receptors},

pubstate = {published},

tppubtype = {article}

}

@article{tauszig-delamasure_drosophila_2002,

title = {Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections},

author = {Servane Tauszig-Delamasure and Hana Bilak and Maria Capovilla and Jules A Hoffmann and Jean-Luc Imler},

doi = {10.1038/ni747},

issn = {1529-2908},

year  = {2002},

date = {2002-01-01},

journal = {Nature Immunology},

volume = {3},

number = {1},

pages = {91--97},

abstract = {We report here the identification and functional characterization of DmMyD88, a gene encoding the Drosophila homolog of mammalian MyD88. DmMyD88 combines a Toll-IL-1R homology (TIR) domain and a death domain. Overexpression of DmMyD88 was sufficient to induce expression of the antifungal peptide Drosomycin, and induction of Drosomycin was markedly reduced in DmMyD88-mutant flies. DmMyD88 interacted with Toll through its TIR domain and required the death domain proteins Tube and Pelle to activate expression of Drs, which encodes Drosomycin. DmMyD88-mutant flies were highly susceptible to infection by fungi and Gram-positive bacteria, but resisted Gram-negative bacterial infection much as did wild-type flies. Phenotypic comparison of DmMyD88-mutant flies and MyD88-deficient mice showed essential differences in the control of Gram-negative infection in insects and mammals.},

keywords = {Adaptor Proteins, Amino Acid, Animals, Antigens, Antimicrobial Cationic Peptides, Cell Surface, Chromosome Mapping, Differentiation, Disease Susceptibility, Enterococcus faecalis, Epistasis, Escherichia coli, Female, Gene Expression Regulation, Genes, Genetic, Genetically Modified, Gram-Negative Bacteria, hoffmann, Hypocreales, imler, Immunologic, Insect, Insect Proteins, M3i, Membrane Glycoproteins, Micrococcus luteus, Myeloid Differentiation Factor 88, Protein Structure, Protein-Serine-Threonine Kinases, Receptors, Recombinant Fusion Proteins, Sequence Alignment, Sequence Homology, Signal Transducing, Tertiary, Toll-Like Receptors, Transfection},

pubstate = {published},

tppubtype = {article}

}