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Transcript
The Antimicrobial Host Defense of Drosophila : A Paradigm for Innate Immunity Jules A.Hoffmann, Institute of Cellular and Molecular Biology, CNRS, Strasbourg, France The fruitfly Drosophila mounts a potent defense reaction during fungal, bacterial and viral infections. We have investigated this defense and have asked three types of questions : (1) how does Drosophila recognize the invading microorganisms; (2) how does recognition lead to activation of intracellular signaling cascades and gene reprogramming; (3) which effector molecules are produced to oppose the microorganisms. Our results point to a sophisticated defense mechanism which is based on several circulating, transmembrane or cytosolic receptors of microbial ligands. Bound receptors trigger several distinct signaling cascades which culminate in the activation of NF-κB family members, which in turn control the expression of hundreds of immune-response genes, some of which have potent antimicrobial activities. Stringent parallels with innate immune mechanisms of mammals point to a common ancestry of this defense and will be discussed in the presentation. Recent Reviews : J.A. HOFFMANN (2003). The Immune Response of Drosophila. Nature, Vol 426, 33-38. LEMAITRE B, HOFFMANN JA (2007). The host defense of Drosophila melanogaster. Annual Review of Immunology. 25:697-743. BEUTLER B, EIDENSCHENK C, CROZAT K, IMLER JL, TAKEUCHI O, HOFFMANN JA, AKIRA S (2007). Genetic analysis of resistance to viral infection. Nature Reviews of Immunology. Vol 7, 753-766. FERRANDON D, IMLER JL, HETRU C, HOFFMANN JA (2007). The Drosophila systemic immune response: sensing and signalling during bacterial and fungal infections. Nature Reviews of Immunology. Vol 7, 862-874.