title: 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-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.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, California, USA.
authors.forename: A Marijke
authors.initials: AM
authors.lastname: Keestra
authors.forename: Maria G
authors.initials: MG
authors.lastname: Winter
authors.forename: Daisy
authors.initials: D
authors.lastname: Klein-Douwel
authors.forename: Mariana N
authors.initials: MN
authors.lastname: Xavier
authors.forename: Sebastian E
authors.initials: SE
authors.lastname: Winter
authors.forename: Anita
authors.initials: A
authors.lastname: Kim
authors.forename: Renée M
authors.initials: RM
authors.lastname: Tsolis
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Bäumler
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D053474:Nod1 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D053473:Nod2 Signaling Adaptor Protein / Q000235:genetics / Q000378:metabolism*; D012480:Salmonella Infections / Q000235:genetics / Q000378:metabolism* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D008840:Microfilament Proteins; D016328:NF-kappa B; D053474:Nod1 Signaling Adaptor Protein; C507873:Nod1 protein, mouse; D053473:Nod2 Signaling Adaptor Protein; C495945:Nod2 protein, mouse; C118287:SipA protein, Salmonella; D037521:Virulence Factors