Immunity—脑膜免疫学重磅突破：脑膜巨噬细胞是大脑对抗新冠病毒感染的先锋军

中文摘要

中枢神经系统（CNS）的表面受到脑膜的保护，脑膜中含有致密的脑膜巨噬细胞（MMs）网络。在此，研究人员研究了组织常驻MM在病毒感染中的作用。MHC-II-MM在新生儿中大量存在，而MHC-II+MM随着时间的推移才会出现。这些脑膜免疫屏障的巨噬细胞对外周病原体及其成分（如LPS、SARS-CoV-2和淋巴细胞性脉络膜脑膜炎病毒（LCMV））有不同的反应。无症状的外周LCMV感染导致脑膜的短暂感染和活化。缺乏巨噬细胞但保留脑小胶质细胞的小鼠，或具有巨噬细胞特异性Stat1或Ifnar缺失的小鼠，表现出中枢神经系统中病毒的广泛播散。使用局部靶向MM的经颅药物耗竭脑膜巨噬细胞导致脑膜的几个区域感染并引起致命性脑膜炎。在LPS攻击或新生儿中出现的MHC-II+MM数量低，与感染时的病毒载量高有关。因此，MMs可保护病毒感染，并可作为中枢神经系统病毒感染的治疗靶点。

英文摘要

The surface of the central nervous system (CNS) is protected by the meninges, which contain a dense network of meningeal macrophages (MMs). Here, we examined the role of tissue-resident MM in viral infection. MHC-II- MM were abundant neonatally, whereas MHC-II+ MM appeared over time. These barrier macrophages differentially responded to in vivo peripheral challenges such as LPS, SARS-CoV-2, and lymphocytic choriomeningitis virus (LCMV). Peripheral LCMV infection, which was asymptomatic, led to a transient infection and activation of the meninges. Mice lacking macrophages but conserving brain microglia, or mice bearing macrophage-specific deletion of Stat1 or Ifnar, exhibited extensive viral spread into the CNS. Transcranial pharmacological depletion strategies targeting MM locally resulted in several areas of the meninges becoming infected and fatal meningitis. Low numbers of MHC-II+ MM, which is seen upon LPS challenge or in neonates, corelated with higher viral load upon infection. Thus, MMs protect against viral infection and may present targets for therapeutic manipulation.

参考文献：Meningeal macrophages protect against viral neuroinfection, Immunity. 2022 Oct 27;S1074-7613(22)00546-5. doi: 10.1016/j.immuni.2022.10.005. Online ahead of print.

微信视频预览查看

打赏