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The Vi capsular polysaccharide enables Salmonella enterica serovar typhi to evade microbe-guided neutrophil chemotaxis.

Wangdi T, Lee CY, Spees AM, Yu C, Kingsbury DD, Winter SE, Hastey CJ, Wilson RP, Heinrich V, Bäumler AJ - PLoS Pathog. (2014)

Bottom Line: Typhimurium) is associated with a localized gastroenteritis in humans.Typhi.Collectively, these data suggest that expression of the virulence-associated (Vi) capsular polysaccharide of S.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States of America.

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.

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The Vi capsular polysaccharide inhibits chemotactic responses of human neutrophils in vitro.(A, B, C, D, E and F) The indicated bacterial strains were immobilized by laser tweezers (arrows) and brought in close proximity to a pipette-held human neutrophil. Video micrographs were taken at the indicated time points. At least four neutrophils were analyzed per blood sample. Each experiment was repeated with neutrophils from four different individuals and one representative example is shown. (A, B and F) Note chemotactic pseudopodia that extend from neutrophils toward bacteria.
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ppat-1004306-g001: The Vi capsular polysaccharide inhibits chemotactic responses of human neutrophils in vitro.(A, B, C, D, E and F) The indicated bacterial strains were immobilized by laser tweezers (arrows) and brought in close proximity to a pipette-held human neutrophil. Video micrographs were taken at the indicated time points. At least four neutrophils were analyzed per blood sample. Each experiment was repeated with neutrophils from four different individuals and one representative example is shown. (A, B and F) Note chemotactic pseudopodia that extend from neutrophils toward bacteria.

Mentions: To study bacterial-guided neutrophil chemotaxis, an initially quiescent human neutrophil was picked up at the tip of a micropipette. Bacteria were then immobilized by a laser optical-trap (laser tweezers) and brought stepwise into close proximity of the neutrophil in the presence of human serum (Fig. S2A). We investigated three organisms that interact differently with the human intestinal mucosa: a commensal organism residing in the intestinal lumen (Escherichia coli strain Nissle 1917), an invasive enteric pathogen associated with a localized gastroenteritis (S. Typhimurium) and the causative agent of an invasive disseminated infection termed typhoid fever (S. Typhi). Bringing E. coli (Fig. 1A, Video S1) or S. Typhimurium (Fig. 1B, S2B, Video S2) into a certain distance of a human neutrophil induced a vigorous chemotactic response, characterized by formation of a cellular pseudopod, which protruded toward the bacteria and responded quickly to their relocation. In striking contrast, S. Typhi did not elicit any chemotactic response by human neutrophils (Fig. 1C, S2C, Video S3).


The Vi capsular polysaccharide enables Salmonella enterica serovar typhi to evade microbe-guided neutrophil chemotaxis.

Wangdi T, Lee CY, Spees AM, Yu C, Kingsbury DD, Winter SE, Hastey CJ, Wilson RP, Heinrich V, Bäumler AJ - PLoS Pathog. (2014)

The Vi capsular polysaccharide inhibits chemotactic responses of human neutrophils in vitro.(A, B, C, D, E and F) The indicated bacterial strains were immobilized by laser tweezers (arrows) and brought in close proximity to a pipette-held human neutrophil. Video micrographs were taken at the indicated time points. At least four neutrophils were analyzed per blood sample. Each experiment was repeated with neutrophils from four different individuals and one representative example is shown. (A, B and F) Note chemotactic pseudopodia that extend from neutrophils toward bacteria.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4125291&req=5

ppat-1004306-g001: The Vi capsular polysaccharide inhibits chemotactic responses of human neutrophils in vitro.(A, B, C, D, E and F) The indicated bacterial strains were immobilized by laser tweezers (arrows) and brought in close proximity to a pipette-held human neutrophil. Video micrographs were taken at the indicated time points. At least four neutrophils were analyzed per blood sample. Each experiment was repeated with neutrophils from four different individuals and one representative example is shown. (A, B and F) Note chemotactic pseudopodia that extend from neutrophils toward bacteria.
Mentions: To study bacterial-guided neutrophil chemotaxis, an initially quiescent human neutrophil was picked up at the tip of a micropipette. Bacteria were then immobilized by a laser optical-trap (laser tweezers) and brought stepwise into close proximity of the neutrophil in the presence of human serum (Fig. S2A). We investigated three organisms that interact differently with the human intestinal mucosa: a commensal organism residing in the intestinal lumen (Escherichia coli strain Nissle 1917), an invasive enteric pathogen associated with a localized gastroenteritis (S. Typhimurium) and the causative agent of an invasive disseminated infection termed typhoid fever (S. Typhi). Bringing E. coli (Fig. 1A, Video S1) or S. Typhimurium (Fig. 1B, S2B, Video S2) into a certain distance of a human neutrophil induced a vigorous chemotactic response, characterized by formation of a cellular pseudopod, which protruded toward the bacteria and responded quickly to their relocation. In striking contrast, S. Typhi did not elicit any chemotactic response by human neutrophils (Fig. 1C, S2C, Video S3).

Bottom Line: Typhimurium) is associated with a localized gastroenteritis in humans.Typhi.Collectively, these data suggest that expression of the virulence-associated (Vi) capsular polysaccharide of S.

View Article: PubMed Central - PubMed

Affiliation: Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States of America.

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.

Show MeSH
Related in: MedlinePlus