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

Angela M Jansen,Lindsay J Hall,Piero Mastroeni,Robert A Kingsley,Simon Clare,Andrew J Grant,Gordon Dougan,David Goulding,Kathryn E Holt,Denise M Monack

doi:10.1371/journal.ppat.1002131

Angela M Jansen, Lindsay J Hall + Show 8 more

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https://doi.org/10.1371/journal.ppat.1002131

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Journal: PLoS Pathogens	Publication Date: Jul 28, 2011
Citations: 70	License type: CC BY 4.0

Affiliation: Wellcome Sanger Institute, University of Cambridge

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.

Highlights

The genus Salmonella comprises serotypes with a range of host adaptation, and spectrum of disease syndromes ranging from selflimiting gastroenteritis, bacteraemia and typhoid fever
Typhimurium expressing Vi polysaccharide resulted in a blunted response in recruitment of NK and PMN cells
This suggested that genes required for Vi biosynthesis are present in C5.507 Vi+, but that the S

Summary

Introduction

The genus Salmonella comprises serotypes with a range of host adaptation, and spectrum of disease syndromes ranging from selflimiting gastroenteritis, bacteraemia and typhoid fever. Typhoid fever is a systemic disease caused by Salmonella enterica serovar Typhi Typhi), a serotype that is highly host-adapted to the human host. Typhoid disease is characterised by a slow onset, protracted fever and a relatively high frequency of chronic carriage [1]. Fever is an important feature of typhoid, progression of the disease is relatively slow and septic shock is uncommon. Pyrogenic cytokines are elevated in typhoid patients [2,3], they are low relative to patients with sepsis [4,5]

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