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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Bacterial Proteins / genetics
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Bacterial Proteins / metabolism*
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Cell Line
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Humans
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Mice
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Mice, Inbred C57BL
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Microfilament Proteins / genetics
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Microfilament Proteins / metabolism*
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NF-kappa B / genetics
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NF-kappa B / metabolism
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Nod1 Signaling Adaptor Protein / genetics
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Nod1 Signaling Adaptor Protein / metabolism*
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Nod2 Signaling Adaptor Protein / genetics
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Nod2 Signaling Adaptor Protein / metabolism*
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Salmonella Infections / genetics
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Salmonella Infections / metabolism*
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Salmonella Infections / microbiology
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Salmonella typhimurium / genetics
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Salmonella typhimurium / metabolism*
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Signal Transduction*
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Virulence Factors / genetics
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Virulence Factors / metabolism*
Substances
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Bacterial Proteins
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Microfilament Proteins
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NF-kappa B
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Nod1 Signaling Adaptor Protein
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Nod1 protein, mouse
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Nod2 Signaling Adaptor Protein
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Nod2 protein, mouse
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SipA protein, Salmonella
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Virulence Factors