Neurons under viral attack: victims or warriors?
Neurons under viral attack: victims or warriors?
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DOI：
10.1016/j.neuint.2010.02.016
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发表时间：
2010-05
影响因子：
4.2
通讯作者：
Basu A
中科院分区：
文献类型：
--
作者：
Chakraborty S;Nazmi A;Dutta K;Basu A
当中枢神经系统(CNS)受到病毒攻击时，必须从CNS本身产生防御性抗病毒反应，以快速有效地遏制感染，并将对敏感、专门和不可再生的神经组织的附带损害降至最低。这是一个独特的挑战，因为完整的血脑屏障(BBB)和缺乏适当的淋巴引流使CNS实际上处于循环免疫细胞的雷达之外，循环免疫细胞一直对周围组织中的抗原保持警惕。与周围组织相比，中枢神经系统细胞的抗原提呈能力有限，这是因为完全缺乏树突状细胞，主要组织相容性复合体(MHC)蛋白在神经元和胶质细胞中的表达很弱。然而，过去二十年的研究已经确定了中枢神经系统固有的免疫效应机制，用于立即处理、减弱和清除病毒感染，并在后期从外周循环以中和抗体和细胞毒T细胞的形式涌入。特殊的中枢神经系统细胞、小胶质细胞和星形胶质细胞被认为是大脑中唯一包含病毒攻击的前哨细胞，但神经元几乎没有被认为是保护自己免受嗜神经病毒增殖和致病的潜在候选细胞。然而，越来越多的证据表明，细胞外刺激导致神经元表达淋巴组织特有的免疫因子。本文旨在全面分析这种条件改变在神经元蛋白表达谱中的研究现状及其在中枢神经系统天然免疫反应中的作用，以对抗病毒感染。
When the central nervous system (CNS) is under viral attack, defensive antiviral responses must necessarily arise from the CNS itself to rapidly and efficiently curb infections with minimal collateral damage to the sensitive, specialized and non-regenerating neural tissue. This presents a unique challenge because an intact blood–brain barrier (BBB) and lack of proper lymphatic drainage keeps the CNS virtually outside the radar of circulating immune cells that are at constant vigilance for antigens in peripheral tissues. Limited antigen presentation skills of CNS cells in comparison to peripheral tissues is because of a total lack of dendritic cells and feeble expression of major histocompatibility complex (MHC) proteins in neurons and glia. However, research over the past two decades has identified immune effector mechanisms intrinsic to the CNS for immediate tackling, attenuating and clearing of viral infections, with assistance pouring in from peripheral circulation in the form of neutralizing antibodies and cytotoxic T cells at a later stage. Specialized CNS cells, microglia and astrocytes, were regarded as sole sentinels of the brain for containing a viral onslaught but neurons held little recognition as a potential candidate for protecting itself from the proliferation and pathogenesis of neurotropic viruses. Accumulating evidence however indicates that extracellular insult causes neurons to express immune factors characteristic of lymphoid tissues. This article aims to comprehensively analyze current research on this conditional alteration in the protein expression repertoire of neurons and the role it plays in CNS innate immune response to counter viral infections.
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