RRC ID 33052
Author Lhocine N, Ribeiro PS, Buchon N, Wepf A, Wilson R, Tenev T, Lemaitre B, Gstaiger M, Meier P, Leulier F.
Title PIMS modulates immune tolerance by negatively regulating Drosophila innate immune signaling.
Journal Cell Host Microbe
Abstract Metazoans tolerate commensal-gut microbiota by suppressing immune activation while maintaining the ability to launch rapid and balanced immune reactions to pathogenic bacteria. Little is known about the mechanisms underlying the establishment of this threshold. We report that a recently identified Drosophila immune regulator, which we call PGRP-LC-interacting inhibitor of Imd signaling (PIMS), is required to suppress the Imd innate immune signaling pathway in response to commensal bacteria. pims expression is Imd (immune deficiency) dependent, and its basal expression relies on the presence of commensal flora. In the absence of PIMS, resident bacteria trigger constitutive expression of antimicrobial peptide genes (AMPs). Moreover, pims mutants hyperactivate AMPs upon infection with Gram-negative bacteria. PIMS interacts with the peptidoglycan recognition protein (PGRP-LC), causing its depletion from the plasma membrane and shutdown of Imd signaling. Therefore, PIMS is required to establish immune tolerance to commensal bacteria and to maintain a balanced Imd response following exposure to bacterial infections.
Volume 4(2)
Pages 147-58
Published 2008-8-14
DOI 10.1016/j.chom.2008.07.004
PII S1931-3128(08)00222-9
PMID 18692774
MeSH Animals Carrier Proteins / genetics Carrier Proteins / metabolism Cells, Cultured Down-Regulation* Drosophila / immunology* Drosophila / microbiology* Drosophila Proteins / genetics Drosophila Proteins / metabolism* Escherichia coli / immunology Escherichia coli / physiology Female Gene Expression Immune Tolerance* Intestines / immunology Intestines / microbiology Intestines / physiology Male Signal Transduction* Transcription Factors / genetics Transcription Factors / metabolism
IF 15.923
Times Cited 153