A Salmonella virulence factor activates the NOD1/NOD2 signaling pathway

A. Marijke Keestra, Maria G. Winter, Daisy Klein-Douwel, Mariana N. Xavier, Sebastian E. Winter, Anita Kim, Renée M. Tsolis, Andreas J. Bäumler

Research output: Contribution to journalArticlepeer-review

46 Scopus citations

Abstract

The invasion-associated type III secretion system (T3SS-1) of Salmonella enterica serotype Typhimurium (S. Typhi-murium) 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.

Original languageEnglish (US)
Article numbere00266-11
JournalmBio
Volume2
Issue number6
DOIs
StatePublished - 2011

ASJC Scopus subject areas

  • Microbiology
  • Virology

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