A Salmonella Virulence Factor Activates the NOD1/NOD2 Signaling Pathway

Overview

Journal mBio

Publisher American Society for Microbiology

Specialty Microbiology

Date 2011 Dec 22

PMID 22186610

Citations 51

Authors

A Marijke Keestra

Maria G Winter

Daisy Klein-Douwel

Mariana N Xavier

Sebastian E Winter

Anita Kim

Renee M Tsolis

Andreas J Baumler

Affiliations

Soon will be listed here.

Abstract

The invasion-associated type III secretion system (T3SS-1) of Salmonella enterica serotype Typhimurium (S. Typhimurium) activates the transcription factor NF-κB in tissue culture cells and induces inflammatory responses in animal models through unknown mechanisms. Here we show that bacterial delivery or ectopic expression of SipA, a T3SS-1-translocated protein, led to the activation of the NOD1/NOD2 signaling pathway and consequent RIP2-mediated induction of NF-κB-dependent inflammatory responses. SipA-mediated activation of NOD1/NOD2 signaling was independent of bacterial invasion in vitro but required an intact T3SS-1. In the mouse colitis model, SipA triggered mucosal inflammation in wild-type mice but not in NOD1/NOD2-deficient mice. These findings implicate SipA-driven activation of the NOD1/NOD2 signaling pathway as a mechanism by which the T3SS-1 induces inflammatory responses in vitro and in vivo.

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