Endothelial Exosome Plays a Functional Role during Rickettsial Infection.
Endothelial Exosome Plays a Functional Role during Rickettsial Infection.
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DOI：
10.1128/mbio.00769-21
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发表时间：
2021-05-11
期刊：
影响因子：
6.4
通讯作者：
Gong B
中科院分区：
文献类型：
--
作者：
Liu Y;Zhou C;Su Z;Chang Q;Qiu Y;Bei J;Gaitas A;Xiao J;Drelich A;Khanipov K;Jin Y;Golovko G;Saito TB;Gong B
斑点热群立克次体病（SFRs）是一种毁灭性的人类传染病。血管内皮细胞（ECs）是立克次体感染的主要目标。在大多数致死性SFR病例中，由EC屏障功能障碍引起的水肿发生在脑和肺，但其潜在机制尚不清楚。该研究的目的是探索立克次体感染的ec衍生外泌体（Exos）在感染过程中的潜在作用。采用大小排斥层析法（SEC），我们从感染立克次体的人脐静脉内皮细胞（HUVECs） （R-ECExos）和感染南立克次体或帕克氏体小鼠（R-plsExos）的血浆中收集条件、过滤、无细菌的培养基中纯化出Exos。我们观察到立克次体感染增加了异质plsExos的释放，但内皮外泌体的大小、形态和产量在感染后没有显著改变。与正常plsExos和ECExos相比，R-plsExos和R-ECExos均可诱导受体正常脑微血管ECs （BMECs）功能障碍。R-plsExos对小鼠受体BMEC屏障功能的影响是剂量依赖性的。R-ECExos对人受体BMEC屏障功能的影响依赖于外泌体RNA货物。新一代测序分析和干环定量逆转录pcr （RT-qPCR）验证表明，立克次体感染触发内皮外泌体mir-23a和mir-30b的选择性富集，其可能靶向内皮屏障。据我们所知，这是关于细胞外囊泡在专性细胞内细菌感染后的功能作用的第一篇报道。
Spotted fever group rickettsioses (SFRs) are devastating human infections. Vascular endothelial cells (ECs) are the primary targets of rickettsial infection. Edema resulting from EC barrier dysfunction occurs in the brain and lungs in most cases of lethal SFR, but the underlying mechanisms remain unclear. The aim of the study was to explore the potential role of Rickettsia-infected, EC-derived exosomes (Exos) during infection. Using size exclusion chromatography (SEC), we purified Exos from conditioned, filtered, bacterium-free media collected from Rickettsia parkeri-infected human umbilical vein ECs (HUVECs) (R-ECExos) and plasma of Rickettsia australis- or R. parkeri-infected mice (R-plsExos). We observed that rickettsial infection increased the release of heterogeneous plsExos, but endothelial exosomal size, morphology, and production were not significantly altered following infection. Compared to normal plsExos and ECExos, both R-plsExos and R-ECExos induced dysfunction of recipient normal brain microvascular ECs (BMECs). The effect of R-plsExos on mouse recipient BMEC barrier function is dose dependent. The effect of R-ECExos on human recipient BMEC barrier function is dependent on the exosomal RNA cargo. Next-generation sequencing analysis and stem-loop quantitative reverse transcription-PCR (RT-qPCR) validation revealed that rickettsial infection triggered the selective enrichment of endothelial exosomal mir-23a and mir-30b, which potentially target the endothelial barrier. To our knowledge, this is the first report on the functional role of extracellular vesicles following infection by obligately intracellular bacteria.