Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections

Nat Immunol. 2002 Jan;3(1):91-7. doi: 10.1038/ni747. Epub 2001 Dec 17.

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.

Publication types

  • Comparative Study

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / physiology*
  • Antimicrobial Cationic Peptides / biosynthesis
  • Antimicrobial Cationic Peptides / genetics
  • Antimicrobial Cationic Peptides / physiology
  • Chromosome Mapping
  • Disease Susceptibility
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / immunology*
  • Drosophila melanogaster / microbiology
  • Enterococcus faecalis / physiology*
  • Epistasis, Genetic
  • Escherichia coli / physiology
  • Female
  • Gene Expression Regulation / physiology*
  • Genes, Insect
  • Gram-Negative Bacteria / physiology
  • Hypocreales / physiology*
  • Insect Proteins / biosynthesis*
  • Insect Proteins / genetics
  • Insect Proteins / physiology
  • Membrane Glycoproteins / physiology
  • Micrococcus luteus / physiology
  • Molecular Sequence Data
  • Myeloid Differentiation Factor 88
  • Protein Structure, Tertiary
  • Protein-Serine-Threonine Kinases / physiology
  • Receptors, Cell Surface*
  • Receptors, Immunologic / genetics
  • Receptors, Immunologic / physiology*
  • Recombinant Fusion Proteins
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Toll-Like Receptors
  • Transfection

Substances

  • Adaptor Proteins, Signal Transducing
  • Antigens, Differentiation
  • Antimicrobial Cationic Peptides
  • Drosophila Proteins
  • Insect Proteins
  • Membrane Glycoproteins
  • Myd88 protein, Drosophila
  • Myeloid Differentiation Factor 88
  • Receptors, Cell Surface
  • Receptors, Immunologic
  • Recombinant Fusion Proteins
  • Tl protein, Drosophila
  • Toll-Like Receptors
  • tub protein, Drosophila
  • DRS protein, Drosophila
  • Mtk protein, Drosophila
  • pll protein, Drosophila
  • Protein-Serine-Threonine Kinases

Associated data

  • GENBANK/AF128403
  • GENBANK/AF422803