A new role for host annexin A2 in establishing bacterial adhesion to vascular endothelial cells: lines of evidence from atomic force microscopy and an in vivo study
A new role for host annexin A2 in establishing bacterial adhesion to vascular endothelial cells: lines of evidence from atomic force microscopy and an in vivo study
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DOI：
10.1038/s41374-019-0284-z
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发表时间：
2019-11-01
影响因子：
5
通讯作者：
Gong, Bin
中科院分区：
文献类型：
--
作者：
He, Xi;Zhang, Weiwei;Gong, Bin
了解细菌粘附对于我们了解血管内细菌感染发病机制的初始阶段具有挑战性且至关重要。血管内皮细胞（EC）是立克次体的主要目标，立克次体是一种专性细胞内细菌，可导致人类和动物严重的全身性疾病。但对于任何细菌来说，在激活之前在流动血液的剪切应力下细菌粘附到 EC 的机制尚不清楚。尽管宿主表面膜联蛋白a2（ANXA2）已被确定参与细菌对上皮细胞的有效侵袭，但在ECs细菌感染领域缺乏直接证据。在本研究中，我们采用一种新颖的、基于解剖学的体内定量细菌粘附血管 EC 系统，结合原子力显微镜 (AFM)，来检查内皮管腔表面 ANXA2 在立克次体粘附 EC 过程中的作用。我们还检查了 ANXA2 抗体是否影响金黄色葡萄球菌与 EC 的结合。我们发现ANXA2的缺失在体外阻碍了立克次体对EC的附着，并在体内阻碍了立克次体对血管腔表面的粘附。 AFM 研究证实 EC 表面 ANXA2 作为立克次体的粘附受体，而立克次体粘附素 OmpB 是相关的细菌配体。此外，用抗ANXA2抗体预处理EC可减少EC表面相关的金黄色葡萄球菌。我们得出的结论是，内皮表面 ANXA2 在启动病原体-宿主相互作用中发挥着重要作用，最终导致细菌锚定在血管腔表面。
Understanding bacterial adhesion is challenging and critical to our understanding of the initial stages of the pathogenesis of endovascular bacterial infections. The vascular endothelial cell (EC) is the main target of Rickettsia, an obligately intracellular bacterium that causes serious systemic disease in humans and animals. But the mechanism(s) underlying bacterial adherence to ECs under shear stress from flowing blood prior to activation are unknown for any bacteria. Although host surface annexin a2 (ANXA2) has been identified to participate in efficient bacterial invasion of epithelial cells, direct evidence is lacking in the field of bacterial infections of ECs. In the present study, we employ a novel, anatomically based, in vivo quantitative bacterial-adhesion-to-vascular-EC system, combined with atomic force microscopy (AFM), to examine the role of endothelial luminal surface ANXA2 during rickettsial adherence to ECs. We also examined whether ANXA2 antibody affected binding of Staphylococcus aureus to ECs. We found that deletion of ANXA2 impeded rickettsial attachment to the ECs in vitro and blocked rickettsial adherence to the blood vessel luminal surface in vivo. The AFM studies established that EC surface ANXA2 acts as an adherence receptor for rickettsiae, and that rickettsial adhesin OmpB is the associated bacterial ligand. Furthermore, pretreatment of ECs with anti-ANXA2 antibody reduced EC surface-associated S. aureus. We conclude that the endothelial surface ANXA2 plays an important role in initiating pathogen-host interactions, ultimately leading to bacterial anchoring on the vascular luminal surface.