Typhoid: Engage Cloaking Mechanism

Salmonella typhimurium Salmonella enterica serovar Typhi (S. Typhi) is a strictly human-adapted pathogen associated with a disseminated febrile illness, termed typhoid fever. In contrast, S. enterica serovar Typhimurium causes an infection that manifests as a localized gastroenteritis in immunocompetent individuals. To control a bacterial infection, neutrophils have to first migrate toward the microbe and then ingest and kill the intruder. Since Salmonella Typhi has a greater ability than S. Typhimurium to spread from its port of entry, researchers investigated whether both pathogens differ in their ability to evade neutrophil chemotaxis.

Surprisingly, S. Typhi, but not S. Typhimurium, inhibited neutrophil chemotaxis. Investigation of the underlying mechanism revealed that microbe-guided chemotaxis proceeded through a C5a- dependent mechanism, which could be blocked by the Vi capsular polysaccharide of S. Typhi. These data suggest that the chemotactic chase of neutrophils is a host defense mechanism operational during gastroenteritis, but not during the initial stages of typhoid fever.

The Vi Capsular Polysaccharide Enables Salmonella enterica Serovar Typhi to Evade Microbe-Guided Neutrophil Chemotaxis. (2014) PLoS Pathog 10(8): e1004306. doi:10.1371/journal.ppat.1004306
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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