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脑膜巨噬细胞对病毒性神经感染起保护作用
作者:小柯机器人 发布时间:2022/11/5 17:09:09

法国艾克斯马赛大学Rejane Rua团队近期取得重要工作进展,他们研究发现脑膜巨噬细胞对病毒性神经感染起保护作用。这一研究成果2022年11月1日在线发表于《免疫学》杂志上。

研究人员鉴定了组织驻留MM在病毒感染中的作用。新生儿时期有大量的MHC-II- MM,而MHC-II+ MM则随着时间的推移而出现。这些屏障巨噬细胞对体内外周挑战如LPS、SARS-CoV-2和淋巴细胞性脉络脑膜炎病毒(LCMV)的反应不同。无症状的外周LCMV感染导致短暂的感染和脑膜激活。缺乏巨噬细胞但保留大脑小胶质细胞的小鼠,或巨噬细胞特异性缺失Stat1Ifnar的小鼠,表现出广泛的病毒扩散到中枢神经系统。

针对局部MM的经颅药理学耗竭策略导致脑膜的几个区域被感染和致命的脑膜炎。在LPS激发试验或新生儿中可见的MHC-II+ MM数量较少,与感染时较高的病毒载量相关。因此,MM可以保护人们免受病毒感染,并可能成为治疗操作的靶点。

据介绍,中枢神经系统(CNS)的表面受脑膜的保护,脑膜中含有密集的脑膜巨噬细胞(MM)网络。

附:英文原文

Title: Meningeal macrophages protect against viral neuroinfection

Author: Julie Rebejac, Elisa Eme-Scolan, Laurie Arnaud Paroutaud, Sarah Kharbouche, Matei Teleman, Lionel Spinelli, Emeline Gallo, Annie Roussel-Queval, Ana Zarubica, Amandine Sansoni, Quentin Bardin, Philippe Hoest, Marie-Cécile Michallet, Carine Brousse, Karine Crozat, Monica Manglani, Zhaoyuan Liu, Florent Ginhoux, Dorian B. McGavern, Marc Dalod, Bernard Malissen, Toby Lawrence, Rejane Rua

Issue&Volume: 2022-11-01

Abstract: The surface of the central nervous system (CNS) is protected by the meninges, whichcontain a dense network of meningeal macrophages (MMs). Here, we examined the roleof 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 infectionand 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 depletionstrategies targeting MM locally resulted in several areas of the meninges becominginfected and fatal meningitis. Low numbers of MHC-II+ MM, which is seen upon LPS challenge or in neonates, corelated with higher viralload upon infection. Thus, MMs protect against viral infection and may present targetsfor therapeutic manipulation.

DOI: 10.1016/j.immuni.2022.10.005

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00546-5

期刊信息

Immunity:《免疫》,创刊于1994年。隶属于细胞出版社,最新IF:21.522
官方网址:https://www.cell.com/immunity/home
投稿链接:https://www.editorialmanager.com/immunity/default.aspx