A <italic toggle="yes">Salmonella</italic> 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-κB in tissue culture cells and induces inflammatory responses in animal models through unknown mechanisms. Here we show that bacteria...

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Autores principales:	A. Marijke Keestra, Maria G. Winter, Daisy Klein-Douwel, Mariana N. Xavier, Sebastian E. Winter, Anita Kim, Renée M. Tsolis, Andreas J. Bäumler
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2011
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/ecf62f74eaf14c21a13ddd59b5ee60b3
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spelling	oai:doaj.org-article:ecf62f74eaf14c21a13ddd59b5ee60b32021-11-15T15:38:48ZA <italic toggle="yes">Salmonella</italic> Virulence Factor Activates the NOD1/NOD2 Signaling Pathway10.1128/mBio.00266-112150-7511https://doaj.org/article/ecf62f74eaf14c21a13ddd59b5ee60b32011-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00266-11https://doaj.org/toc/2150-7511ABSTRACT 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. IMPORTANCE Salmonella enterica serotype Typhimurium (S. Typhimurium) deploys a type III secretion system (T3SS-1) to induce intestinal inflammation and benefits from the ensuing host response, which enhances growth of the pathogen in the intestinal lumen. However, the mechanisms by which the T3SS-1 triggers inflammatory responses have not been resolved. Here we show that the T3SS-1 effector protein SipA induces NF-κB activation and intestinal inflammation by activating the NOD1/NOD2 signaling pathway. These data suggest that the T3SS-1 escalates innate responses through a SipA-mediated activation of pattern recognition receptors in the host cell cytosol.A. Marijke KeestraMaria G. WinterDaisy Klein-DouwelMariana N. XavierSebastian E. WinterAnita KimRenée M. TsolisAndreas J. BäumlerAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 2, Iss 6 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 A. Marijke Keestra Maria G. Winter Daisy Klein-Douwel Mariana N. Xavier Sebastian E. Winter Anita Kim Renée M. Tsolis Andreas J. Bäumler A <italic toggle="yes">Salmonella</italic> Virulence Factor Activates the NOD1/NOD2 Signaling Pathway
description	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. IMPORTANCE Salmonella enterica serotype Typhimurium (S. Typhimurium) deploys a type III secretion system (T3SS-1) to induce intestinal inflammation and benefits from the ensuing host response, which enhances growth of the pathogen in the intestinal lumen. However, the mechanisms by which the T3SS-1 triggers inflammatory responses have not been resolved. Here we show that the T3SS-1 effector protein SipA induces NF-κB activation and intestinal inflammation by activating the NOD1/NOD2 signaling pathway. These data suggest that the T3SS-1 escalates innate responses through a SipA-mediated activation of pattern recognition receptors in the host cell cytosol.
format	article
author	A. Marijke Keestra Maria G. Winter Daisy Klein-Douwel Mariana N. Xavier Sebastian E. Winter Anita Kim Renée M. Tsolis Andreas J. Bäumler
author_facet	A. Marijke Keestra Maria G. Winter Daisy Klein-Douwel Mariana N. Xavier Sebastian E. Winter Anita Kim Renée M. Tsolis Andreas J. Bäumler
author_sort	A. Marijke Keestra
title	A <italic toggle="yes">Salmonella</italic> Virulence Factor Activates the NOD1/NOD2 Signaling Pathway
title_short	A <italic toggle="yes">Salmonella</italic> Virulence Factor Activates the NOD1/NOD2 Signaling Pathway
title_full	A <italic toggle="yes">Salmonella</italic> Virulence Factor Activates the NOD1/NOD2 Signaling Pathway
title_fullStr	A <italic toggle="yes">Salmonella</italic> Virulence Factor Activates the NOD1/NOD2 Signaling Pathway
title_full_unstemmed	A <italic toggle="yes">Salmonella</italic> Virulence Factor Activates the NOD1/NOD2 Signaling Pathway
title_sort	<italic toggle="yes">salmonella</italic> virulence factor activates the nod1/nod2 signaling pathway
publisher	American Society for Microbiology
publishDate	2011
url	https://doaj.org/article/ecf62f74eaf14c21a13ddd59b5ee60b3
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A <italic toggle="yes">Salmonella</italic> Virulence Factor Activates the NOD1/NOD2 Signaling Pathway

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