A Salmonella Typhimurium-Typhi Genomic Chimera: A Model to Study Vi Polysaccharide Capsule Function In Vivo

PLoS Pathogens

Andrew J. Grant¹  Piero Mastroeni¹  Lindsay J. Hall²  David Goulding²  Robert A. Kingsley²  Simon Clare²  Gordon Dougan²  Kathryn E. Holt²  Angela M. Jansen² 

[1] Department of Veterinary Medicine, University of Cambridge, Cambridge, United Kingdom;The Wellcome Trust Sanger Institute, The Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom

关键词: Salmonella typhimurium;    Salmonella typhi;    NK cells;    Spleen;    Cytokines;    Polysaccharides;    Immune response;    Immune cells;   

DOI  :  10.1371/journal.ppat.1002131

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY