School of Agriculture, Biomedicine and Environment, La Trobe University, Melbourne, VIC, Australia.
School of Life and Environmental Sciences, Charles Perkins Centre and the Institute for Infectious Diseases, The University of Sydney, Sydney, NSW, Australia.
Front Immunol. 2022 Nov 15;13:1044721. doi: 10.3389/fimmu.2022.1044721. eCollection 2022.
The central nervous system (CNS) is a constitutive structure of various cell types conserved by anatomical barriers. Many of the major CNS cell-type populations distributed across the different brain regions are targets for several neurotropic viruses. Numerous studies have demonstrated that viral susceptibility within the CNS is not absolute and initiates a cell-type specific antiviral defence response. Neurons, astrocytes, and microglial cells are among the major resident cell populations within the CNS and are all equipped to sense viral infection and induce a relative antiviral response mostly through type I IFN production, however, not all these cell types adopt a similar antiviral strategy. Rising evidence has suggested a diversity regarding IFN production and responsiveness based on the cell type/sub type, regional distinction and cell`s developmental state which could shape distinct antiviral signatures. Among CNS resident cell types, neurons are of the highest priority to defend against the invading virus due to their poor renewable nature. Therefore, infected and uninfected glial cells tend to play more dominant antiviral roles during a viral infection and have been found to be the major CNS IFN producers. Alternatively, neuronal cells do play an active part during antiviral responses but may adopt differential strategies in addition to induction of a typical type I IFN response, to minimize the chance of cellular damage. Heterogeneity observed in neuronal IFN responsiveness may be partially explained by their altered ISGs and/or lower STATS expression levels, however, further studies are required to fully elucidate the specificity of the acquired antiviral responses by distinct CNS cell types.
中枢神经系统(CNS)是由解剖屏障保守的各种细胞类型的固有结构。分布在不同脑区的许多主要 CNS 细胞类型群体都是几种神经病毒的靶标。许多研究表明,CNS 内的病毒易感性并非绝对,而是会引发细胞类型特异性的抗病毒防御反应。神经元、星形胶质细胞和小胶质细胞是 CNS 内主要的常驻细胞群体之一,它们都能够感知病毒感染并通过产生 I 型 IFN 来诱导相对的抗病毒反应,但并非所有这些细胞类型都采用类似的抗病毒策略。越来越多的证据表明,基于细胞类型/亚型、区域差异和细胞发育状态,IFN 的产生和反应存在多样性,这可能形成不同的抗病毒特征。在 CNS 常驻细胞类型中,由于神经元的可再生性较差,因此它们是抵御入侵病毒的首要任务。因此,感染和未感染的神经胶质细胞在病毒感染期间往往发挥更主导的抗病毒作用,并且已被发现是 CNS 中主要的 IFN 产生细胞。相反,神经元细胞在抗病毒反应中确实发挥了积极的作用,但除了诱导典型的 I 型 IFN 反应外,它们可能还会采用不同的策略,以最大程度地减少细胞损伤的机会。神经元 IFN 反应性的异质性部分可以通过其改变的 ISGs 和/或更低的 STAT 表达水平来解释,但是,需要进一步的研究来充分阐明不同 CNS 细胞类型获得的抗病毒反应的特异性。