Salmonella-induced thrombi in mice develop asynchronously in the spleen and liver and are not effective bacterial traps
Salmonella-induced thrombi in mice develop asynchronously in the spleen and liver and are not effective bacterial traps
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DOI：
10.1182/blood-2018-08-867267
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发表时间：
2019-02-07
期刊：
影响因子：
20.3
通讯作者：
Cunningham, Adam F.
中科院分区：
文献类型：
--
作者：
Beristain-Covarrubias, Nonantzin;Perez-Toledo, Marisol;Cunningham, Adam F.
血栓形成是与多器官损伤相关的全身感染的常见、危及生命的并发症。我们之前描述了小鼠鼠伤寒沙门氏菌感染诱导炎症驱动血栓形成的新机制。感染后 7 天，肝脏中形成血栓，并在感染消退后持续存在，并且是单核细胞依赖性的。出乎意料的是，此时脾脏中的血栓形成并不明显，尽管其细菌负担与肝脏相似。在这项研究中，我们表明血栓形成确实发生在脾脏中，但与肝脏相比，血栓形成的动力学显着加快，24 小时内就很明显，随后迅速消退。血栓形成和细菌负荷的独特动力学提供了对以下假设的检验：健康血管中形成血栓以捕获或清除循环中的细菌，通常称为免疫血栓形成。值得注意的是，尽管在感染早期在受感染的脾脏和肝脏中检测到了细菌，但组织切片的免疫组织学分析表明血栓中的细菌数量非常少。相比之下，细菌存在于沙门氏菌体外诱导的整个血小板聚集体中。因此，我们证明血栓形成具有器官特异性动力学，并挑战了免疫血栓形成作为体内捕获细菌机制的普遍性。
Thrombosis is a frequent, life-threatening complication of systemic infection associated with multiple organ damage. We have previously described a novel mechanism of inflammation-driven thrombosis induced by Salmonella Typhimurium infection of mice. Thrombosis in the liver develops 7 days after infection, persisting after the infection resolves, and is monocytic cell dependent. Unexpectedly, thrombosis was not prominent in the spleen at this time, despite carrying a similar bacterial burden as the liver. In this study, we show that thrombosis does occur in the spleen but with strikingly accelerated kinetics compared with the liver, being evident by 24 hours and resolving rapidly thereafter. The distinct kinetics of thrombosis and bacterial burden provides a test of the hypothesis that thrombi form in healthy vessels to trap or remove bacteria from the circulation, often termed immunothrombosis. Remarkably, despite bacteria being detected throughout infected spleens and livers in the early days of infection, immunohistological analysis of tissue sections show that thrombi contain very low numbers of bacteria. In contrast, bacteria are present throughout platelet aggregates induced by Salmonella in vitro. Therefore, we show that thrombosis develops with organ-specific kinetics and challenge the universality of immunothrombosis as a mechanism to capture bacteria in vivo.