title: Salmonella enterica Serovar Typhi conceals the invasion-associated type three secretion system from the innate immune system by gene regulation.
abstract: Delivery of microbial products into the mammalian cell cytosol by bacterial secretion systems is a strong stimulus for triggering pro-inflammatory host responses. Here we show that Salmonella enterica serovar Typhi (S. Typhi), the causative agent of typhoid fever, tightly regulates expression of the invasion-associated type III secretion system (T3SS-1) and thus fails to activate these innate immune signaling pathways. The S. Typhi regulatory protein TviA rapidly repressed T3SS-1 expression, thereby preventing RAC1-dependent, RIP2-dependent activation of NF-κB in epithelial cells. Heterologous expression of TviA in S. enterica serovar Typhimurium (S. Typhimurium) suppressed T3SS-1-dependent inflammatory responses generated early after infection in animal models of gastroenteritis. These results suggest that S. Typhi reduces intestinal inflammation by limiting the induction of pathogen-induced processes through regulation of virulence gene expression.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States of America.
authors.forename: Sebastian E
authors.initials: SE
authors.lastname: Winter
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States of America.
authors.forename: Maria G
authors.initials: MG
authors.lastname: Winter
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States of America.
authors.forename: Victor
authors.initials: V
authors.lastname: Poon
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States of America.
authors.forename: A Marijke
authors.initials: AM
authors.lastname: Keestra
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States of America.
authors.forename: Torsten
authors.initials: T
authors.lastname: Sterzenbach
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States of America.
authors.forename: Franziska
authors.initials: F
authors.lastname: Faber
authors.affiliation: Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Luciana F
authors.initials: LF
authors.lastname: Costa
authors.affiliation: Departamento de Clinica e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Fabiane
authors.initials: F
authors.lastname: Cassou
authors.affiliation: Departamento de Clinica e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Erica A
authors.initials: EA
authors.lastname: Costa
authors.affiliation: Departamento de Clinica e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Geraldo E S
authors.initials: GE
authors.lastname: Alves
authors.affiliation: Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Tatiane A
authors.initials: TA
authors.lastname: Paixão
authors.affiliation: Departamento de Clinica e Cirurgia Veterinárias, Escola de Veterinária, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Renato L
authors.initials: RL
authors.lastname: Santos
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States of America.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Bäumler
mesh_terms: D000818:Animals; D058947:Bacterial Secretion Systems / Q000235:genetics / Q000276:immunology*; D002417:Cattle; D004195:Disease Models, Animal; D005759:Gastroenteritis / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D015964:Gene Expression Regulation, Bacterial / Q000235:genetics / Q000276:immunology; D006367:HeLa Cells; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D012485:Salmonella typhi / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D014435:Typhoid Fever / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D037521:Virulence Factors / Q000235:genetics / Q000276:immunology*
chemical_list: D058947:Bacterial Secretion Systems; D037521:Virulence Factors