Decreased antiviral immune response within the central nervous system of aged mice is associated with increased lethality of West Nile virus encephalitis.
Decreased antiviral immune response within the central nervous system of aged mice is associated with increased lethality of West Nile virus encephalitis.
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DOI：
10.1111/acel.13412
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发表时间：
2021-08
期刊：
影响因子：
7.8
通讯作者：
Klein RS
中科院分区：
文献类型：
--
作者：
Funk KE;Arutyunov AD;Desai P;White JP;Soung AL;Rosen SF;Diamond MS;Klein RS
西尼罗河病毒（WNV）是一种新兴的病原体，可引起从轻度流感样疾病到脑炎的疾病综合征。虽然西尼罗河病毒感染的发病率在各年龄组之间相当一致，但致命性脑炎的风险随着年龄的增长而增加。先前的研究已经证明了年龄相关的功能性免疫缺陷限制了全身抗病毒免疫并增加了死亡率;然而，年龄对中枢神经系统（CNS）内抗病毒免疫应答的影响尚不清楚。在这里，我们发现，老年小鼠表现出增加的外周器官和中枢神经系统组织的病毒负荷，后者是与骨髓和淋巴细胞的活化与类似感染的年轻动物相比，改变。老年小鼠表现出小胶质细胞的MHCII表达较低，CNS中WNV特异性CD 8 + T细胞和CD 8 + CD 45+细胞的PD 1水平较高，IFNγ表达水平较低。这些数据表明，老年中枢神经系统表现出有限的局部再活化的T细胞在病毒性脑炎，这可能会导致减少病毒控制在这个网站。西尼罗河病毒（WNV）是一种新出现的病原体，在高龄个体中具有较高的致死性脑炎风险。在这里，我们发现，老年小鼠表现出增加的外周器官和中枢神经系统组织的病毒负荷，后者是与骨髓和淋巴细胞的活化与类似感染的年轻动物相比，改变。
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. West Nile virus (WNV) is an emerging pathogen with a higher risk of lethal encephalitis in individuals with advanced age. 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.
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影响因子：
9.3
作者：
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影响因子：
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