The Drosophila immune response against Gram-negative bacteria is mediated by a peptidoglycan recognition protein

Marie Gottar, Vanessa Gobert, Tatiana Michel, Marcia Belvin, Geoffrey Duyk, Jules A. Hoffmann, Dominique Ferrandon () and Julien Royet ()
Additional contact information
Marie Gottar: Institut de Biologie Moléculaire et Cellulaire
Vanessa Gobert: Institut de Biologie Moléculaire et Cellulaire
Tatiana Michel: Institut de Biologie Moléculaire et Cellulaire
Marcia Belvin: Exelixis Inc.
Geoffrey Duyk: Exelixis Inc.
Jules A. Hoffmann: Institut de Biologie Moléculaire et Cellulaire
Dominique Ferrandon: Institut de Biologie Moléculaire et Cellulaire
Julien Royet: Institut de Biologie Moléculaire et Cellulaire

Nature, 2002, vol. 416, issue 6881, 640-644

Abstract: Abstract The antimicrobial defence of Drosophila relies largely on the challenge-induced synthesis of an array of potent antimicrobial peptides by the fat body1,2. The defence against Gram-positive bacteria and natural fungal infections is mediated by the Toll signalling pathway, whereas defence against Gram-negative bacteria is dependent on the Immune deficiency (IMD) pathway3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18. Loss-of-function mutations in either pathway reduce the resistance to corresponding infections3,9. The link between microbial infections and activation of these two pathways has remained elusive. The Toll pathway is activated by Gram-positive bacteria through a circulating Peptidoglycan recognition protein (PGRP-SA)6. PGRPs appear to be highly conserved from insects to mammals, and the Drosophila genome contains 13 members19,20,21,22,23. Here we report a mutation in a gene coding for a putative transmembrane protein, PGRP-LC, which reduces survival to Gram-negative sepsis but has no effect on the response to Gram-positive bacteria or natural fungal infections. By genetic epistasis, we demonstrate that PGRP-LC acts upstream of the imd gene. The data on PGRP-SA with respect to the response to Gram-positive infections, together with the present report, indicate that the PGRP family has a principal role in sensing microbial infections in Drosophila.

Date: 2002
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DOI: 10.1038/nature734

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