Yersinia pestis escapes entrapment in thrombi by targeting platelet function.
Yersinia pestis escapes entrapment in thrombi by targeting platelet function.
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DOI：
10.1111/jth.15065
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发表时间：
2020-12
期刊：
影响因子：
--
通讯作者：
Koupenova M
中科院分区：
文献类型：
--
作者：
Palace SG;Vitseva O;Proulx MK;Freedman JE;Goguen JD;Koupenova M
血小板在止血和血栓形成中的作用是公认的经典。最近的研究表明，血小板也可以执行多种免疫功能。血小板的双重血栓形成和免疫作用表明，它们可能对细胞外细菌的复制或传播构成屏障。然而，一些血源性病原体，如鼠疫耶尔森氏菌，通常会达到病原体传播所必需的高血管滴度。目前尚不清楚病原体如何或是否绕过血小板屏障以阻止细菌传播和复制。我们试图确定细胞外血源性细菌病原体是否积极干扰血小板功能，使用鼠疫菌作为模型系统。采用聚集法、免疫荧光法和扫描电镜检测了人血小板与多种转基因鼠疫菌菌株的相互作用和形态变化。鼠疫耶尔森菌直接破坏血小板血栓的稳定性，防止纤维蛋白/血小板凝块中的细菌包裹。这种活性依赖于两种特征明确的细菌毒力因子：鼠疫菌纤溶酶原激活剂Pla，它刺激宿主介导的纤维蛋白溶解；细菌III型分泌系统（T3SS），它将细菌蛋白传递到目标宿主细胞的细胞质中，以减少或阻止有效的免疫反应。被鼠疫杆菌T3SS中毒的血小板不能对血栓前刺激做出反应，T3SS的表达减少了血小板血栓中中性粒细胞胞外陷阱的形成。这些发现是首次证明细菌病原体使用其T3SS和内源性蛋白酶来操纵血小板功能并逃避血小板血栓的捕获。
Platelets are classically recognized for their role in hemostasis and thrombosis. Recent work has demonstrated that platelets can also execute a variety of immune functions. The dual prothrombotic and immunological roles of platelets suggest that they may pose a barrier to the replication or dissemination of extracellular bacteria. However, some bloodborne pathogens, such as the plague bacterium Yersinia pestis, routinely achieve high vascular titers that are necessary for pathogen transmission. It is not currently known how or if pathogens circumvent platelet barriers to bacterial dissemination and replication. We sought to determine whether extracellular bloodborne bacterial pathogens actively interfere with platelet function, using Y pestis as a model system. The interactions and morphological changes of human platelets with various genetically modified Y pestis strains were examined using aggregation assays, immunofluorescence, and scanning electron microscopy. Yersinia pestis directly destabilized platelet thrombi, preventing bacterial entrapment in fibrin/platelet clots. This activity was dependent on two well-characterized bacterial virulence factors: the Y pestis plasminogen activator Pla, which stimulates host-mediated fibrinolysis, and the bacterial type III secretion system (T3SS), which delivers bacterial proteins into the cytoplasm of targeted host cells to reduce or prevent effective immunological responses. Platelets intoxicated by the Y pestis T3SS were unable to respond to prothrombotic stimuli, and T3SS expression decreased the formation of neutrophil extracellular traps in platelet thrombi. These findings are the first demonstration of a bacterial pathogen using its T3SS and an endogenous protease to manipulate platelet function and to escape entrapment in platelet thrombi.
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影响因子：
6.7
作者：
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通讯作者：
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发表时间：
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