title: The Vi capsular polysaccharide enables Salmonella enterica serovar typhi to evade microbe-guided neutrophil chemotaxis.
abstract: 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.
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States of America.
authors.forename: Tamding
authors.initials: T
authors.lastname: Wangdi
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, Davis, California, United States of America.
authors.forename: Cheng-Yuk
authors.initials: CY
authors.lastname: Lee
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States of America.
authors.forename: Alanna M
authors.initials: AM
authors.lastname: Spees
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, Davis, California, United States of America.
authors.forename: Chenzhou
authors.initials: C
authors.lastname: Yu
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States of America.
authors.forename: Dawn D
authors.initials: DD
authors.lastname: Kingsbury
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States of America.
authors.forename: Sebastian E
authors.initials: SE
authors.lastname: Winter
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, Davis, California, United States of America.
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Hastey
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States of America.
authors.forename: R Paul
authors.initials: RP
authors.lastname: Wilson
authors.affiliation: Department of Biomedical Engineering, University of California, Davis, Davis, California, United States of America.
authors.forename: Volkmar
authors.initials: V
authors.lastname: Heinrich
authors.affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States of America.
authors.forename: Andreas J
authors.initials: AJ
authors.lastname: Bäumler
mesh_terms: D000818:Animals; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D015936:Complement C5a / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D051379:Mice; D020556:Neutrophil Infiltration / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D044087:Receptor, Anaphylatoxin C5a / Q000276:immunology; D012485:Salmonella typhi / Q000276:immunology*; D012486:Salmonella typhimurium / Q000276:immunology; D014435:Typhoid Fever / Q000276:immunology*
chemical_list: D011135:Polysaccharides, Bacterial; D044087:Receptor, Anaphylatoxin C5a; C054154:capsular polysaccharide, Salmonella; D015936:Complement C5a
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