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 journalArticle

40 Citations (Scopus)

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)
JournalmBio
Volume2
Issue number6
DOIs
StatePublished - Nov 2011

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Virulence Factors
Salmonella
Salmonella enterica
Colitis
Transcription Factors
Animal Models
Cell Culture Techniques
Inflammation
Proteins
In Vitro Techniques

ASJC Scopus subject areas

  • Microbiology
  • Virology

Cite this

Marijke Keestra, A., Winter, M. G., Klein-Douwel, D., Xavier, M. N., Winter, S. E., Kim, A., ... Bäumler, A. J. (2011). A Salmonella virulence factor activates the NOD1/NOD2 signaling pathway. mBio, 2(6). https://doi.org/10.1128/mBio.00266-11

A Salmonella virulence factor activates the NOD1/NOD2 signaling pathway. / Marijke Keestra, A.; Winter, Maria G.; Klein-Douwel, Daisy; Xavier, Mariana N.; Winter, Sebastian E.; Kim, Anita; Tsolis, Renée M.; Bäumler, Andreas J.

In: mBio, Vol. 2, No. 6, 11.2011.

Research output: Contribution to journalArticle

Marijke Keestra, A, Winter, MG, Klein-Douwel, D, Xavier, MN, Winter, SE, Kim, A, Tsolis, RM & Bäumler, AJ 2011, 'A Salmonella virulence factor activates the NOD1/NOD2 signaling pathway', mBio, vol. 2, no. 6. https://doi.org/10.1128/mBio.00266-11
Marijke Keestra A, Winter MG, Klein-Douwel D, Xavier MN, Winter SE, Kim A et al. A Salmonella virulence factor activates the NOD1/NOD2 signaling pathway. mBio. 2011 Nov;2(6). https://doi.org/10.1128/mBio.00266-11
Marijke Keestra, A. ; Winter, Maria G. ; Klein-Douwel, Daisy ; Xavier, Mariana N. ; Winter, Sebastian E. ; Kim, Anita ; Tsolis, Renée M. ; Bäumler, Andreas J. / A Salmonella virulence factor activates the NOD1/NOD2 signaling pathway. In: mBio. 2011 ; Vol. 2, No. 6.
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