Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein

Tatiana Michel, Jean Marc Relchhart, Jules A. Hoffmann, Julien Royet

Research output: Contribution to journalArticleResearchpeer-review

635 Citations (Scopus)


Microbial infection activates two distinct intracellular signalling cascades in the immune-responsive fat body of Drosophila1, 2. Gram-positive bacteria and fungi predominantly induce the Toll signalling pathway, whereas Gram-negative bacteria activate the Imd pathway3, 4. Loss-of-function mutants in either pathway reduce the resistance to corresponding infections4, 5. Genetic screens have identified a range of genes involved in these intracellular signalling cascades6-12, 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.

Original languageEnglish
Pages (from-to)756-759
Number of pages4
Issue number6865
Publication statusPublished - 13 Dec 2001
Externally publishedYes


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