RRC ID 30674
Author Michel T, Reichhart JM, Hoffmann JA, Royet J.
Title Drosophila Toll is activated by Gram-positive bacteria through a circulating peptidoglycan recognition protein.
Journal Nature
Abstract Microbial infection activates two distinct intracellular signalling cascades in the immune-responsive fat body of Drosophila. Gram-positive bacteria and fungi predominantly induce the Toll signalling pathway, whereas Gram-negative bacteria activate the Imd pathway. Loss-of-function mutants in either pathway reduce the resistance to corresponding infections. Genetic screens have identified a range of genes involved in these intracellular signalling cascades, 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, Spätzle, 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 receptors 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.
Volume 414(6865)
Pages 756-9
Published 2001-12-13
DOI 10.1038/414756a
PII 414756a
PMID 11742401
MeSH Amino Acid Sequence Animals Anti-Bacterial Agents Anti-Infective Agents / metabolism Bacillus thuringiensis Carrier Proteins / blood Carrier Proteins / genetics* Carrier Proteins / metabolism Chromosome Mapping Drosophila / genetics Drosophila / immunology Drosophila / metabolism Drosophila / microbiology* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Enterococcus faecalis Fungi / immunology Fungi / metabolism Genes, Insect Gram-Positive Bacteria / immunology Gram-Positive Bacteria / metabolism* Hemolymph Humans Insect Proteins / genetics Insect Proteins / physiology Membrane Glycoproteins / genetics Membrane Glycoproteins / metabolism* Micrococcus luteus Molecular Sequence Data Mutation Receptors, Cell Surface Sequence Homology, Amino Acid Toll-Like Receptors
IF 43.07
Times Cited 442