title: A Salmonella Typhimurium-Typhi genomic chimera: a model to study Vi polysaccharide capsule function in vivo.
abstract: The Vi capsular polysaccharide is a virulence-associated factor expressed by Salmonella enterica serotype Typhi but absent from virtually all other Salmonella serotypes. In order to study this determinant in vivo, we characterised a Vi-positive S. Typhimurium (C5.507 Vi(+)), harbouring the Salmonella pathogenicity island (SPI)-7, which encodes the Vi locus. S. Typhimurium C5.507 Vi(+) colonised and persisted in mice at similar levels compared to the parent strain, S. Typhimurium C5. However, the innate immune response to infection with C5.507 Vi(+) and SGB1, an isogenic derivative not expressing Vi, differed markedly. Infection with C5.507 Vi(+) resulted in a significant reduction in cellular trafficking of innate immune cells, including PMN and NK cells, compared to SGB1 Vi(-) infected animals. C5.507 Vi(+) infection stimulated reduced numbers of TNF-α, MIP-2 and perforin producing cells compared to SGB1 Vi(-). The modulating effect associated with Vi was not observed in MyD88(-/-) and was reduced in TLR4(-/-) mice. The presence of the Vi capsule also correlated with induction of the anti-inflammatory cytokine IL-10 in vivo, a factor that impacted on chemotaxis and the activation of immune cells in vitro.
authors.affiliation: The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
authors.forename: Angela M
authors.initials: AM
authors.lastname: Jansen
authors.forename: Lindsay J
authors.initials: LJ
authors.lastname: Hall
authors.forename: Simon
authors.initials: S
authors.lastname: Clare
authors.forename: David
authors.initials: D
authors.lastname: Goulding
authors.forename: Kathryn E
authors.initials: KE
authors.lastname: Holt
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Grant
authors.forename: Piero
authors.initials: P
authors.lastname: Mastroeni
authors.forename: Gordon
authors.initials: G
authors.lastname: Dougan
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kingsley
mesh_terms: D000818:Animals; D016667:Bacterial Capsules / Q000235:genetics / Q000276:immunology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D056426:Genetic Loci / Q000276:immunology; D044404:Genomic Islands / Q000235:genetics / Q000276:immunology; D007113:Immunity, Innate; D051379:Mice; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000235:genetics / Q000276:immunology; D012485:Salmonella typhi / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000276:immunology; D014435:Typhoid Fever / Q000235:genetics / Q000276:immunology
chemical_list: D016207:Cytokines; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D011135:Polysaccharides, Bacterial; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4