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

Nature Immunology volume 3, pages 91–97 (2002)Cite this article

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.

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Figure 1: The Drosophila genome encodes a MyD88-related molecule.
Figure 2: DmMyD88 specifically induces the Drs promoter in transfected S2 cells.
Figure 3: DmMyD88 selectively associates with Toll through its TIR domain.
Figure 4: Constitutive expression of Drs and Mtk in transgenic flies overexpressing DmMyD88 in the fat body.
Figure 5: Expression of antimicrobial peptide genes in DmMyD88-mutant flies.
Figure 6: DmMyD88-mutant flies are extremely sensitive to fungal and Gram-positive bacterial infection.

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Acknowledgements

We thank R. O. Clauss, E. Santiago, R. Syllas and C. Chevalier for expert technical support; D. Ferrandon and P. Ligoxigakis for critical reading of the manuscript; our colleagues for stimulating discussions and suggestions; R. Medzhitov for sharing unpublished information; and the Bloomington Stock Center for fly strains. Supported by grants from the Centre National de la Recherche Scientifique, the Ministère de l'Education Nationale de la Recherche et de la Technologie, the National Institutes of Health, EntoMed (Strasbourg, France) and Exelixis (San Francisco, CA).

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  1. UPR9022 du Centre National de la Recherche Scientifique, Institut de Biologie Moléculaire et Cellulaire, 15, rue René Descartes, Strasbourg, 67000, France

    Servane Tauszig-Delamasure, Hana Bilak, Maria Capovilla, Jules A. Hoffmann & Jean-Luc Imler

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Correspondence to Jean-Luc Imler.

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Tauszig-Delamasure, S., Bilak, H., Capovilla, M. et al. Drosophila MyD88 is required for the response to fungal and Gram-positive bacterial infections. Nat Immunol 3, 91–97 (2002). https://doi.org/10.1038/ni747

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