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A Salmonella virulence factor activates the NOD1/NOD2 signaling pathway.

ABSTRACT: The invasion-associated type III secretion system (T3SS-1) of Salmonella enterica serotype Typhimurium (S. Typhimurium) activates the transcription factor NF-?B 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-?B-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.

SUBMITTER: Keestra AM

PROVIDER: S-EPMC3238304 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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A Salmonella virulence factor activates the NOD1/NOD2 signaling pathway.

Keestra A Marijke AM Winter Maria G MG Klein-Douwel Daisy D Xavier Mariana N MN Winter Sebastian E SE Kim Anita A Tsolis Renée M RM Bäumler Andreas J AJ

mBio 20111220 6

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 response ...[more]

PMID: 22186610

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