title: The flagellar regulator TviA reduces pyroptosis by Salmonella enterica serovar Typhi.
abstract: To discern virulent from innocuous microbes, the innate immune system senses events associated with bacterial access to immunoprivileged sites such as the host cell cytosol. One such pathway is triggered by the cytosolic delivery of flagellin, the major subunit of the flagellum, by bacterial secretion systems. This leads to inflammasome activation and subsequent proinflammatory cell death (pyroptosis) of the infected phagocyte. In this study, we demonstrate that the causative agent of typhoid fever, Salmonella enterica serovar Typhi, can partially subvert this critical innate immune recognition event. The transcriptional regulator TviA, which is absent from Salmonella serovars associated with human gastroenteritis, repressed the expression of flagellin during infection of human macrophage-like (THP-1) cells. This mechanism allowed S. Typhi to dampen inflammasome activation, leading to reduced interleukin-1β (IL-1β) secretion and diminished cell death. Likewise, the introduction of the tviA gene in nontyphoidal Salmonella enterica serovar Typhimurium reduced flagellin-induced pyroptosis. These data suggest that gene regulation of virulence factors enables S. Typhi to evade innate immune recognition by concealing a pathogen-induced process from being sensed by the inflammasome.
authors: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, USA Sebastian.Winter@UTSouthwestern.edu.
authors: Sebastian E
authors: http://orcid.org/0000-0003-1532-9178
authors: SE
authors: Winter
authors: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, USA.
authors: Maria G
authors: MG
authors: Winter
authors: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, USA.
authors: Vidya
authors: V
authors: Atluri
authors: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, USA.
authors: Victor
authors: V
authors: Poon
authors: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, USA.
authors: Everton L
authors: EL
authors: Romão
authors: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, USA.
authors: Renée M
authors: RM
authors: Tsolis
authors: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, USA.
authors: Andreas J
authors: AJ
authors: Bäumler
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins / Q000276:immunology; D001426:Bacterial Proteins / Q000235:genetics / Q000276:immunology*; D058947:Bacterial Secretion Systems; D001854:Bone Marrow Cells / Q000276:immunology / Q000382:microbiology; D002135:Calcium-Binding Proteins / Q000276:immunology; D002460:Cell Line; D005408:Flagellin / Q000096:biosynthesis*; D015964:Gene Expression Regulation, Bacterial; D006801:Humans; D058847:Inflammasomes / Q000276:immunology; D053583:Interleukin-1beta / Q000378:metabolism; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D012485:Salmonella typhi / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology*; D037521:Virulence Factors / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D001426:Bacterial Proteins; D058947:Bacterial Secretion Systems; D002135:Calcium-Binding Proteins; C508585:IL1B protein, human; D058847:Inflammasomes; D053583:Interleukin-1beta; C512299:Ipaf protein, mouse; D014157:Transcription Factors; D037521:Virulence Factors; C098634:tviA protein, Salmonella typhi; D005408:Flagellin
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