Watanabe Rihito, Kakizaki Masatoshi
Department of Bioinformatics, Faculty of Engineering, Soka University, Hachioji, Japan.
Neuropathology. 2017 Aug;37(4):311-320. doi: 10.1111/neup.12374. Epub 2017 Mar 20.
During the early phase of infection with an extremely neurovirulent murine coronavirus, cl-2, the ER-TR7 antigen (ERag)-positive fibers (ERfibs) associated with laminin and collagen III show a rapid increase in expression levels in the meninges, followed by an appearance of the antigens in the ventricle and brain parenchyma. Then, cl-2 invades the ventricle and ventricular wall along the newly assembled ERfibs after infection, using them as a pathway from the meninges, the initial site of infection. In the lymph nodes and spleen, ERag is mainly produced by fibroblastic reticular cells (FRCs), which play a key role in nursing the ERfibs to form a fibroblastic reticular network (FRN). The FRN functions as a conduit system to transfer antigens, cytokines or leukocytes in the lymphoid organs. In the brain parenchyma, astrocytes were found to produce the main components of mature ERfibs, such as collagen, laminin and ERag, which have been identified in the lymphoid organs. The producibility of these extracellular matrices (ECMs) by astrocytes was further confirmed by primary brain cultures, which disclosed the dissociation of laminin and ERag production, and the close association of ERag production with that of collagen, forming a fibrous structure. The pattern of ECM production in vitro indicated the process of forming mature ERfibs in the brain, that is, fibers made of collagen fibers and ERag are wrapped by laminin prepared as a sheet structure. In addition, the brain parenchymal cells that produce interferon β after infection in spite of their residence away from the sites of viral invasion were surrounded by ERfibs, which were closely associated with astrocytic fibers. These findings indicate that astrocytes play a central role in forming the astrocytic reticular network (ARN) in the brain parenchyma, as FRCs do to form FRN in the lymphoid organs.
在感染极具神经毒性的鼠冠状病毒cl-2的早期阶段，与层粘连蛋白和III型胶原相关的ER-TR7抗原（ERag）阳性纤维（ERfibs）在脑膜中的表达水平迅速升高，随后这些抗原出现在脑室和脑实质中。然后，cl-2在感染后沿着新组装的ERfibs侵入脑室和室壁，将其作为从感染初始部位脑膜而来的途径。在淋巴结和脾脏中，ERag主要由成纤维网状细胞（FRCs）产生，这些细胞在滋养ERfibs以形成成纤维网状网络（FRN）中起关键作用。FRN作为一种管道系统，在淋巴器官中转运抗原、细胞因子或白细胞。在脑实质中，发现星形胶质细胞产生成熟ERfibs的主要成分，如胶原、层粘连蛋白和ERag，这些成分已在淋巴器官中得到鉴定。原代脑培养进一步证实了星形胶质细胞产生这些细胞外基质（ECM）的能力，该培养揭示了层粘连蛋白和ERag产生的解离，以及ERag产生与胶原产生的紧密关联，形成了一种纤维结构。体外ECM产生模式表明了脑中成熟ERfibs的形成过程，即由胶原纤维和ERag构成的纤维被制备成片状结构的层粘连蛋白包裹。此外，尽管感染后产生干扰素β的脑实质细胞远离病毒入侵部位，但它们被ERfibs包围，这些ERfibs与星形胶质纤维紧密相关。这些发现表明，星形胶质细胞在脑实质中形成星形胶质网状网络（ARN）方面发挥着核心作用，就像FRCs在淋巴器官中形成FRN一样。
