Streptolysin S Inhibits Neutrophil Recruitment during the Early Stages of Streptococcus pyogenes Infection
Streptolysin S Inhibits Neutrophil Recruitment during the Early Stages of Streptococcus pyogenes Infection
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DOI：
10.1128/iai.00420-09
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发表时间：
2009-11-01
影响因子：
3.1
通讯作者：
Caparon, Michael G.
中科院分区：
文献类型：
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作者：
Lin, Ada;Loughman, Jennifer A.;Caparon, Michael G.
与浅表组织的感染相反，化脓性链球菌感染深层组织可与显著减弱的炎症反应相关，表明该细菌具有促进和抑制炎症的能力。为了验证这一点，我们分析了S。化脓性链球菌突变体的细胞溶解毒素链球菌溶血素S（SLS-）的表达缺陷，并评估的事件发生在感染的最初几个小时内，通过使用几种模型，包括注射斑马鱼（成人，幼虫，和胚胎），经上皮多形核白细胞（PMN）迁移试验，和双光子显微镜的小鼠体内。与野生型S.在化脓性链球菌中，SLS突变体与嗜中性粒细胞的稳健募集相关，并显著降低了成年斑马鱼的致死性肌炎。同样，突变体在胚胎中导致致死的能力减弱。幼虫肌肉的感染允许在真实的时间内对炎症进行分析，这表明突变体已经将PMNs募集到感染部位。体外跨上皮迁移分析表明，SLS抑制宿主细胞产生中性粒细胞趋化信号，这与不相关的溶细胞毒素链球菌溶血素O的促炎作用形成对比。在小鼠体内使用双光子显微镜，我们发现，与野生型S.化脓总之，这些数据支持SLS在S.化脓性感染
In contrast to infection of superficial tissues, Streptococcus pyogenes infection of deeper tissue can be associated with a significantly diminished inflammatory response, suggesting that this bacterium has the ability to both promote and suppress inflammation. To examine this, we analyzed the behavior of an S. pyogenes mutant deficient in expression of the cytolytic toxin streptolysin S (SLS-) and evaluated events that occur during the first few hours of infection by using several models including injection of zebrafish (adults, larvae, and embryos), a transepithelial polymorphonuclear leukocyte (PMN) migration assay, and two-photon microscopy of mice in vivo. In contrast to wild-type S. pyogenes, the SLS- mutant was associated with the robust recruitment of neutrophils and significantly reduced lethal myositis in adult zebrafish. Similarly, the mutant was attenuated in embryos in its ability to cause lethality. Infection of larva muscle allowed an analysis of inflammation in real time, which revealed that the mutant had recruited PMNs to the infection site. Analysis of transepithelial migration in vitro suggested that SLS inhibited the host cells' production of signals chemotactic for neutrophils, which contrasted with the proinflammatory effect of an unrelated cytolytic toxin, streptolysin O. Using two-photon microscopy of mice in vivo, we showed that the extravasation of neutrophils during infection with SLS- mutant bacteria was significantly accelerated compared to infection with wild-type S. pyogenes. Taken together, these data support a role for SLS in the inhibition of neutrophil recruitment during the early stages of S. pyogenes infection.