West Nile virus (WNV) is an emerging pathogen that causes disease syndromes ranging from a mild flu-like illness to encephalitis. While the incidence of WNV infection is fairly uniform across age groups, the risk of lethal encephalitis increases with advanced age. Prior studies have demonstrated age-related, functional immune deficits that limit systemic antiviral immunity and increase mortality; however, the effect of age on antiviral immune responses specifically within the central nervous system (CNS) is unknown. Here, we show that aged mice exhibit increased peripheral organ and CNS tissue viral burden, the latter of which is associated with alterations in activation of both myeloid and lymphoid cells compared with similarly infected younger animals. Aged mice exhibit lower MHCII expression by microglia, and higher levels of PD1 and lower levels of IFNγ expression by WNV-specific CD8⁺ T cells in the CNS and CD8⁺CD45⁺ cells. These data indicate that the aged CNS exhibits limited local reactivation of T cells during viral encephalitis, which may lead to reduced virologic control at this site.

中文翻译：

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老年小鼠中枢神经系统内抗病毒免疫反应降低与西尼罗病毒脑炎致死率增加有关

西尼罗河病毒 (WNV) 是一种新出现的病原体，可引起从轻度流感样疾病到脑炎等疾病综合征。虽然 WNV 感染的发病率在各个年龄组中相当一致，但致死性脑炎的风险随着年龄的增长而增加。先前的研究表明，与年龄相关的功能性免疫缺陷会限制全身抗病毒免疫并增加死亡率；然而，年龄对特别是中枢神经系统 (CNS) 内的抗病毒免疫反应的影响尚不清楚。在这里，我们显示老年小鼠的外周器官和中枢神经系统组织病毒负荷增加，与类似感染的年轻动物相比，后者与骨髓和淋巴细胞活化的改变有关。老年小鼠的小胶质细胞表现出较低的 MHCII 表达，⁺ CNS 中的 T 细胞和 CD8 ⁺ CD45 ⁺细胞。这些数据表明，老年中枢神经系统在病毒性脑炎期间表现出有限的 T 细胞局部再激活，这可能导致该部位的病毒学控制降低。