Wangdi Tamding, Lee Cheng-Yuk, Spees Alanna M, Yu Chenzhou, Kingsbury Dawn D, Winter Sebastian E, Hastey Christine J, Wilson R Paul, Heinrich Volkmar, Bäumler Andreas J
Department of Medical Microbiology and Immunology, School of Medicine, University of California, Davis, Davis, California, United States of America.
Department of Biomedical Engineering, University of California, Davis, Davis, California, United States of America.
PLoS Pathog. 2014 Aug 7;10(8):e1004306. doi: 10.1371/journal.ppat.1004306. eCollection 2014 Aug.
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.
伤寒沙门氏菌血清型伤寒杆菌（伤寒杆菌）可引起伤寒热，这是一种播散性感染，而密切相关的病原体鼠伤寒沙门氏菌血清型鼠伤寒杆菌（鼠伤寒杆菌）则与人类局部性肠胃炎有关。在此，我们使用单细胞实验方法研究了这两种病原体在诱导中性粒细胞趋化反应方面是否存在差异。令人惊讶的是，中性粒细胞会向大肠杆菌和鼠伤寒杆菌伸出趋化伪足，但不会向伤寒杆菌伸出。细菌引导的趋化作用取决于补体成分5a（C5a）和C5a受体（C5aR）的存在。伤寒杆菌荚膜生物合成基因的缺失显著增强了中性粒细胞在体外的趋化反应。此外，荚膜生物合成基因的缺失通过一种依赖C5aR的机制增强了伤寒杆菌在体内与中性粒细胞的关联。总体而言，这些数据表明伤寒杆菌毒力相关（Vi）荚膜多糖的表达阻碍了细菌引导的中性粒细胞趋化作用。
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