Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1

A. Marijke Keestra, Maria G. Winter, Josef J. Auburger, Simon P. Fräßle, Mariana N. Xavier, Sebastian E. Winter, Anita Kim, Victor Poon, Mariëtta M. Ravesloot, Julian F T Waldenmaier, Renée M. Tsolis, Richard A. Eigenheer, Andreas J. Bäumler

Research output: Contribution to journalArticle

120 Citations (Scopus)

Abstract

Our innate immune system distinguishes microbes from self by detecting conserved pathogen-associated molecular patterns. However, these are produced by all microbes, regardless of their pathogenic potential. To distinguish virulent microbes from those with lower disease-causing potential the innate immune system detects conserved pathogen-induced processes, such as the presence of microbial products in the host cytosol, by mechanisms that are not fully resolved. Here we show that NOD1 senses cytosolic microbial products by monitoring the activation state of small Rho GTPases. Activation of RAC1 and CDC42 by bacterial delivery or ectopic expression of SopE, a virulence factor of the enteric pathogen Salmonella, triggered the NOD1 signalling pathway, with consequent RIP2 (also known as RIPK2)-mediated induction of NF-κB- dependent inflammatory responses. Similarly, activation of the NOD1 signalling pathway by peptidoglycan required RAC1 activity. Furthermore, constitutively active forms of RAC1, CDC42 and RHOA activated the NOD1 signalling pathway. Our data identify the activation of small Rho GTPases as a pathogen-induced process sensed through the NOD1 signalling pathway.

Original languageEnglish (US)
Pages (from-to)233-237
Number of pages5
JournalNature
Volume496
Issue number7444
DOIs
StatePublished - Apr 11 2013

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rho GTP-Binding Proteins
Monomeric GTP-Binding Proteins
Immune System
Peptidoglycan
Virulence Factors
Salmonella
Cytosol
Ectopic Gene Expression
Pathogen-Associated Molecular Pattern Molecules

ASJC Scopus subject areas

  • General

Cite this

Keestra, A. M., Winter, M. G., Auburger, J. J., Fräßle, S. P., Xavier, M. N., Winter, S. E., ... Bäumler, A. J. (2013). Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1. Nature, 496(7444), 233-237. https://doi.org/10.1038/nature12025

Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1. / Keestra, A. Marijke; Winter, Maria G.; Auburger, Josef J.; Fräßle, Simon P.; Xavier, Mariana N.; Winter, Sebastian E.; Kim, Anita; Poon, Victor; Ravesloot, Mariëtta M.; Waldenmaier, Julian F T; Tsolis, Renée M.; Eigenheer, Richard A.; Bäumler, Andreas J.

In: Nature, Vol. 496, No. 7444, 11.04.2013, p. 233-237.

Research output: Contribution to journalArticle

Keestra, AM, Winter, MG, Auburger, JJ, Fräßle, SP, Xavier, MN, Winter, SE, Kim, A, Poon, V, Ravesloot, MM, Waldenmaier, JFT, Tsolis, RM, Eigenheer, RA & Bäumler, AJ 2013, 'Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1', Nature, vol. 496, no. 7444, pp. 233-237. https://doi.org/10.1038/nature12025
Keestra AM, Winter MG, Auburger JJ, Fräßle SP, Xavier MN, Winter SE et al. Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1. Nature. 2013 Apr 11;496(7444):233-237. https://doi.org/10.1038/nature12025
Keestra, A. Marijke ; Winter, Maria G. ; Auburger, Josef J. ; Fräßle, Simon P. ; Xavier, Mariana N. ; Winter, Sebastian E. ; Kim, Anita ; Poon, Victor ; Ravesloot, Mariëtta M. ; Waldenmaier, Julian F T ; Tsolis, Renée M. ; Eigenheer, Richard A. ; Bäumler, Andreas J. / Manipulation of small Rho GTPases is a pathogen-induced process detected by NOD1. In: Nature. 2013 ; Vol. 496, No. 7444. pp. 233-237.
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