1. Institut de Biologie Moléculaire et Cellulaire, UPR 9022 du CNRS, 15 rue René Descartes, 67084 Strasbourg cedex, France

Correspondence to: Julien Royet Correspondence and requests for materials should be addressed to J.R. (e-mail: Email: J.Royet@ibmc.u-strasbg.fr).

Abstract

Microbial infection activates two distinct intracellular signalling cascades in the immune-responsive fat body of Drosophila^{1, 2}. Gram-positive bacteria and fungi predominantly induce the Toll signalling pathway, whereas Gram-negative bacteria activate the Imd pathway^{3, 4}. Loss-of-function mutants in either pathway reduce the resistance to corresponding infections^{4, 5}. Genetic screens have identified a range of genes involved in these intracellular signalling cascades^{6, 7, 8, 9, 10, 11, 12}, but how they are activated by microbial infection is largely unknown. Activation of the transmembrane receptor Toll requires a proteolytically cleaved form of an extracellular cytokine-like polypeptide, Spätzle¹³, suggesting that Toll does not itself function as a bona fide recognition receptor of microbial patterns. This is in apparent contrast with the mammalian Toll-like receptors¹⁴ and raises the question of which host molecules actually recognize microbial patterns to activate Toll through Spätzle. Here we present a mutation that blocks Toll activation by Gram-positive bacteria and significantly decreases resistance to this type of infection. The mutation semmelweis (seml) inactivates the gene encoding a peptidoglycan recognition protein (PGRP-SA). Interestingly, seml does not affect Toll activation by fungal infection, indicating the existence of a distinct recognition system for fungi to activate the Toll pathway.

1. Institut de Biologie Moléculaire et Cellulaire, UPR 9022 du CNRS, 15 rue René Descartes, 67084 Strasbourg cedex, France

Correspondence to: Julien Royet Correspondence and requests for materials should be addressed to J.R. (e-mail: Email: J.Royet@ibmc.u-strasbg.fr).