Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections.
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.
Tauszig-Delamasure
Servane
S
UPR9022 du Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, 15, rue René Descartes, 67000 Strasbourg, France.
Bilak
Hana
H
Capovilla
Maria
M
Hoffmann
Jules A
JA
Imler
Jean-Luc
JL
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D030801:Animals, Genetically Modified; D000943:Antigens, Differentiation / Q000235:genetics / Q000502:physiology*; D023181:Antimicrobial Cationic Peptides / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology; D002874:Chromosome Mapping; D004198:Disease Susceptibility; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000235:genetics / Q000276:immunology* / Q000382:microbiology; D013293:Enterococcus faecalis / Q000502:physiology*; D004843:Epistasis, Genetic; D004926:Escherichia coli / Q000502:physiology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D017344:Genes, Insect; D006090:Gram-Negative Bacteria / Q000502:physiology; D006999:Hypocreales / Q000502:physiology*; D019476:Insect Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology; D016982:Micrococcus luteus / Q000502:physiology; D008969:Molecular Sequence Data; D053594:Myeloid Differentiation Factor 88; D017346:Protein Serine-Threonine Kinases / Q000502:physiology; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D051193:Toll-Like Receptors; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D000943:Antigens, Differentiation; D023181:Antimicrobial Cationic Peptides; D029721:Drosophila Proteins; D019476:Insect Proteins; D008562:Membrane Glycoproteins; C499312:Myd88 protein, Drosophila; D053594:Myeloid Differentiation Factor 88; D011956:Receptors, Cell Surface; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; C068721:Tl protein, Drosophila; D051193:Toll-Like Receptors; C084727:tub protein, Drosophila; C091227:DRS protein, Drosophila; C096696:Mtk protein, Drosophila; C079896:pll protein, Drosophila; D017346:Protein Serine-Threonine Kinases