The Vi Capsular Polysaccharide Enables Salmonella enterica Serovar Typhi to Evade Microbe-Guided Neutrophil Chemotaxis

PLoS Pathogens

Christine J. Hastey¹  Cheng-Yuk Lee¹  Volkmar Heinrich¹  Chenzhou Yu¹  Tamding Wangdi²  Sebastian E. Winter²  Andreas J. Bäumler²  Dawn D. Kingsbury²  Alanna M. Spees²  R. Paul Wilson² 

[1] Department of Biomedical Engineering, University of California, Davis, Davis, California, United States of America;Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States of America

关键词: Neutrophils;    Salmonella typhi;    Chemotaxis;    Polysaccharides;    Salmonella typhimurium;    Complement activation;    Mouse models;    Complement inhibitors;   

DOI  :  10.1371/journal.ppat.1004306

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

Salmonella enterica serovar Typhi (S. Typhi) causes typhoid fever, a disseminated infection, while the closely related pathogen S. enterica serovar Typhimurium (S. Typhimurium) is associated with a localized gastroenteritis in humans. Here we investigated whether both pathogens differ in the chemotactic response they induce in neutrophils using a single-cell experimental approach. Surprisingly, neutrophils extended chemotactic pseudopodia toward Escherichia coli and S. Typhimurium, but not toward S. Typhi. Bacterial-guided chemotaxis was dependent on the presence of complement component 5a (C5a) and C5a receptor (C5aR). Deletion of S. Typhi capsule biosynthesis genes markedly enhanced the chemotactic response of neutrophils in vitro. Furthermore, deletion of capsule biosynthesis genes heightened the association of S. Typhi with neutrophils in vivo through a C5aR-dependent mechanism. Collectively, these data suggest that expression of the virulence-associated (Vi) capsular polysaccharide of S. Typhi obstructs bacterial-guided neutrophil chemotaxis.

【 授权许可】

CC BY