title: Salmonella enterica serovar Typhi impairs CD4 T cell responses by reducing antigen availability.
abstract: Salmonella enterica serovar Typhi is associated with a disseminated febrile illness in humans, termed typhoid fever, while Salmonella enterica serovar Typhimurium causes localized gastroenteritis in immunocompetent individuals. One of the genetic differences between both pathogens is the presence in S. Typhi of TviA, a regulatory protein that shuts down flagellin (FliC) expression when bacteria transit from the intestinal lumen into the intestinal mucosa. Here we investigated the consequences of TviA-mediated flagellum gene regulation on flagellin-specific CD4 T cell responses in a mouse model of S. Typhimurium infection. Introduction of the S. Typhi tviA gene into S. Typhimurium suppressed antigen presentation of dendritic cells to flagellin-specific CD4 T cells in vitro. Furthermore, TviA-mediated repression of flagellin expression impaired the activation and proliferation of naive flagellin-specific CD4 T cells in Peyer's patches and mesenteric lymph nodes, which was accompanied by increased bacterial dissemination to the spleen. We conclude that TviA-mediated repression of flagellin expression reduces antigen availability, thereby weakening flagellin-specific CD4 T cell responses.
authors.affiliation: Center for Comparative Medicine, Department of Anatomy, Physiology and Cell Biology, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.
authors.forename: Shaikh M
authors.initials: SM
authors.lastname: Atif
authors.forename: Sebastian E
authors.initials: SE
authors.lastname: Winter
authors.forename: Maria G
authors.initials: MG
authors.lastname: Winter
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: McSorley
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Bäumler
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism*; D058491:Bacterial Load; D001426:Bacterial Proteins / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D004195:Disease Models, Animal; D005408:Flagellin / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D051379:Mice; D008810:Mice, Inbred C57BL; D012480:Salmonella Infections / Q000276:immunology*; D012485:Salmonella typhi / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology*; D014157:Transcription Factors / Q000502:physiology
chemical_list: D000942:Antigens, Bacterial; D001426:Bacterial Proteins; D014157:Transcription Factors; C098634:tviA protein, Salmonella typhi; D005408:Flagellin