Instituto de Inmunología, Genética y Metabolismo, Consejo Nacional de Investigaciones Científicas y Técnicas, Universidad de Buenos Aires, Buenos Aires, Argentina.
Instituto de Medicina Experimental, Consejo Nacional de Investigaciones Científicas y Técnicas-Academia Nacional de Medicina, Buenos Aires, Argentina.
Front Cell Infect Microbiol. 2018 Jun 14;8:200. doi: 10.3389/fcimb.2018.00200. eCollection 2018.
Neurobrucellosis is an inflammatory disease caused by the invasion of spp. to the central nervous system (CNS). The pathogenesis of the disease is not well characterized; however, for to gain access to the brain parenchyma, traversing of the blood-brain barrier (BBB) must take place. To understand the CNS determinants of the pathogenesis of , we have used the BBB model of human brain microvascular endothelial cells (HBMEC) to study the interactions between and brain endothelial cells. In this study, we showed that is able to adhere and invade HBMEC which was dependent on microtubules, microfilaments, endosome acidification and de novo protein synthesis. After infection, rapidly escapes the endosomal compartment of HBMEC and forms a replicative -containing vacuole that involves interactions with the endoplasmic reticulum. Despite the ability of to invade and replicate in HBMEC, the bacterium was unable by itself to traverse HBMEC, but could traverse polarized HBMEC monolayers within infected monocytes. Importantly, infected monocytes that traversed the HBMEC monolayer were a bacterial source for infection of glial cells. This is the first demonstration of the mechanism whereby is able to traverse the BBB and infect cells of the CNS. These results may have important implications in our understanding of the pathogenesis of neurobrucellosis.
神经布鲁氏菌病是一种由 spp. 入侵中枢神经系统（CNS）引起的炎症性疾病。该疾病的发病机制尚未得到很好的描述；然而，为了使进入大脑实质，必须发生血脑屏障（BBB）的穿越。为了了解 的中枢神经系统发病机制决定因素，我们使用了人脑微血管内皮细胞（HBMEC）的 BBB 模型来研究 与脑内皮细胞之间的相互作用。在这项研究中，我们表明 能够黏附和入侵 HBMEC，这依赖于微管、微丝、内体酸化和从头蛋白质合成。感染后， 迅速从 HBMEC 的内体区室逃逸，并形成一个涉及与内质网相互作用的复制性包含空泡。尽管 能够入侵和在 HBMEC 中复制，但该细菌本身无法穿越 HBMEC，而是可以在感染的单核细胞内穿越极化的 HBMEC 单层。重要的是，穿越 HBMEC 单层的感染单核细胞是 感染神经胶质细胞的细菌来源。这是首次证明 能够穿越 BBB 并感染中枢神经系统细胞的机制。这些结果可能对我们理解神经布鲁氏菌病的发病机制具有重要意义。
