title: The Salmonella enterica serotype Typhi regulator TviA reduces interleukin-8 production in intestinal epithelial cells by repressing flagellin secretion.
abstract: Unlike non-typhoidal Salmonella serotypes, S. enterica serotype Typhi does not elicit neutrophilic infiltrates in the human intestinal mucosa. The Vi capsule-encoding tviABCDEvexABCDE operon (viaB locus) is a S. Typhi-specific DNA region preventing production of interleukin (IL)-8 during infection of intestinal epithelial cells. We elucidated the mechanism by which the viaB locus reduces IL-8 production in human colonic epithelial (T84) cells. A S. Typhi tviABCDEvexABCDE deletion mutant, but not a tviBCDEvexABCDE deletion mutant, elicited increased IL-8 production, which could be reduced to wild-type levels by introducing the cloned tviA regulatory gene. Thus, IL-8 expression in T84 cells was modulated by the TviA regulatory protein, but not by the Vi capsular antigen. Consistent with previous reports, IL-8 secretion by T84 cells was dependent on the presence of the flagellin protein FliC. TviA reduced expression of flhDC::lacZ and fliC::lacZ transcriptional fusions and secretion of FliC in S. Typhi. Introduction of tviA into S. enterica serotype Typhimurium reduced flagellin secretion and IL-8 expression. In conclusion, the viaB locus reduces IL-8 production in T84 cells by a TviA-mediated repression of flagellin secretion. Our data suggest that changes in flagella gene regulation played an important role during evolution of the human-adapted S. Typhi.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Ave., Davis, CA, USA.
authors.forename: Sebastian E
authors.initials: SE
authors.lastname: Winter
authors.forename: Manuela
authors.initials: M
authors.lastname: Raffatellu
authors.forename: R Paul
authors.initials: RP
authors.lastname: Wilson
authors.forename: Holger
authors.initials: H
authors.lastname: Rüssmann
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Bäumler
mesh_terms: D019677:Artificial Gene Fusion; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D015536:Down-Regulation; D004847:Epithelial Cells / Q000382:microbiology*; D005408:Flagellin / Q000096:biosynthesis*; D017930:Genes, Reporter; D005816:Genetic Complementation Test; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis*; D012485:Salmonella typhi / Q000235:genetics / Q000276:immunology*; D012486:Salmonella typhimurium / Q000235:genetics; D017384:Sequence Deletion; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D001616:beta-Galactosidase / Q000096:biosynthesis / Q000235:genetics
chemical_list: D001426:Bacterial Proteins; D016209:Interleukin-8; D014157:Transcription Factors; C098634:tviA protein, Salmonella typhi; D005408:Flagellin; D001616:beta-Galactosidase