Innate Immunity : From Flies to Humans. Jules A. Hoffmann. IBMC, University of Strasbourg, Strasbourg, France.

   Insects make up some 80% of all extant species on earth and present a formidable challenge : they put one third of humanity at risk of severe diseases, through their role as vectors of pathogens. They destroy one third of human crops, adding severe strains to humans and livestock. Insects have long been known to be strongly resistant to infections. The mechanisms underlying this resistance, other than the well known process of phagocytosis, have only been addressed relatively recently. A general picture of these defences has now evolved and Drosophila is to be credited for this progress. Remarkably, the unravelling of the Drosophila antimicrobial defences has had a significant impact on understanding essential facets of mammalian immunity. It has also led to a renewed interest in innate immunity, a long neglected field in the study of antimicrobial defences in general.The presentation will review the major developments in the study of host defences in flies over the last decades. A particular emphasis will be put on the identification of effector polypeptides with various antimicrobial activity spectra, on the control of expression of the corresponding genes, on the recognition mechanisms of infecting agents and the activation of intracellular signalling cascades by these receptors. This progress will be put in parallel to that of studies performed in various laboratories on mammalian immune defences. In particular, the contribution of the Drosophila model to our present understanding of innate immunity, from sea anemones to humans, will be highlighted. Further reading : Lemaitre B, Nicolas E, Michaut L, Reichhart JM, Hoffmann JA. Cell. 1996; 86 :973. Hoffmann JA, Kafatos FC, Janeway CA, Ezekowitz RA. Science. 1999; 284: 1313. Hoffmann JA. Nature. 2003; 426: 33. Hultmark D. Curr Opin Immunol. 2003; 15: 12. Ferrandon D, Imler JL, Hetru C, Hoffmann JA. Nat Rev Immunol. 2007; 7: 862. Lemaitre B, Hoffmann J. Annu Rev Immunol. 2007; 25: 697. Kemp C et al J. Immunol. 2012 in press Ganesan S, Aggarwal K, Paquette N, Silverman N. Curr Top Microbiol Immunol. 2011; 349: 25. Kawai T, Akira S. Immunity. 2011; 34: 637. Royet J, Gupta D, Dziarski R. Nat Rev Immunol. 2011; 11: 837.