Microglia play a major role in direct viral-induced demyelination.

Microglia play a major role in direct viral-induced demyelination.
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DOI:
10.1155/2013/510396
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发表时间:
2013
影响因子:
--
通讯作者:
Das Sarma J
Das Sarma J
中科院分区:
其他
文献类型:
--
作者:
Chatterjee D;Biswas K;Nag S;Ramachandra SG;Das Sarma J

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小胶质细胞是中枢神经系统(CNS)中的常驻巨噬细胞样群体。小胶质细胞保持静止,不能执行效应和抗原呈递(APC)功能,直到被损伤或感染激活,并已被建议代表CNS的第一道防线。先前的研究表明,小胶质细胞可以被嗜神经性小鼠肝炎病毒(MHV)持续感染,其导致脑膜脑炎、伴有随后轴突缺失的肌萎缩和脱髓鞘,并作为病毒诱导的人类神经系统疾病多发性硬化症(MS)的模型。目前的研究表明,MHV感染与急性炎症期间小胶质细胞的显著活化相关,如细胞形态的特征性变化和小胶质细胞特异性蛋白Iba 1(离子化钙结合衔接分子1)表达增加所证明的,Iba 1是巨噬细胞/小胶质细胞特异性的新型钙结合蛋白,参与膜皱褶和吞噬作用。在慢性炎症(感染后30天),小胶质细胞仍然存在于脱髓鞘区域。在离体脊髓切片培养和体外新生儿小胶质细胞培养中进行的实验证实了直接小胶质细胞感染。我们的研究结果表明,MHV可以直接感染和激活小胶质细胞在急性炎症,这反过来在慢性炎症阶段引起髓鞘的吞噬作用,导致慢性炎症脱髓鞘。
Microglia are the resident macrophage-like populations in the central nervous system (CNS). Microglia remain quiescent, unable to perform effector and antigen presentation (APC) functions until activated by injury or infection, and have been suggested to represent the first line of defence for the CNS. Previous studies demonstrated that microglia can be persistently infected by neurotropic mouse hepatitis virus (MHV) which causes meningoencephalitis, myelitis with subsequent axonal loss, and demyelination and serve as a virus-induced model of human neurological disease multiple sclerosis (MS). Current studies revealed that MHV infection is associated with the pronounced activation of microglia during acute inflammation, as evidenced by characteristic changes in cellular morphology and increased expression of microglia-specific proteins, Iba1 (ionized calcium-binding adaptor molecule 1), which is a macrophage/microglia-specific novel calcium-binding protein and involved in membrane ruffling and phagocytosis. During chronic inflammation (day 30 postinfection), microglia were still present within areas of demyelination. Experiments performed in ex vivo spinal cord slice culture and in vitro neonatal microglial culture confirmed direct microglial infection. Our results suggest that MHV can directly infect and activate microglia during acute inflammation, which in turn during chronic inflammation stage causes phagocytosis of myelin sheath leading to chronic inflammatory demyelination.
增强的绿色荧光蛋白表达可用于监测体外和小鼠中枢神经系统中鼠冠状病毒的扩散。
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