Neuronal CXCL10 directs CD8+ T-cell recruitment and control of West Nile virus encephalitis
Neuronal CXCL10 directs CD8+ T-cell recruitment and control of West Nile virus encephalitis
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DOI：
10.1128/jvi.79.17.11457-11466.2005
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发表时间：
2005-09-01
影响因子：
5.4
通讯作者：
Diamond, MS
中科院分区：
文献类型：
--
作者：
Klein, RS;Lin, E;Diamond, MS
抗原特异性CD8（+）T细胞的激活和进入中枢神经系统是从感染的神经元中清除西尼罗河病毒（WNV）的重要步骤。负责病毒特异性T细胞定向迁移的分子信号及其细胞来源目前尚不清楚。在这里，我们证明，在响应WNV感染，神经元分泌趋化因子CXCL10，通过趋化因子受体CXCR3招募效应T细胞。CXCL10的中和或遗传缺陷导致CXCR3（+）CD8（+）T细胞运输减少，大脑中病毒负荷增加，发病率和死亡率增加。这些数据支持了趋化因子神经生物学的新范式，因为神经元通常不被认为产生抗病毒免疫应答，并且CXCL10可能代表了响应中枢神经系统中的WNV感染的新型神经保护剂。
The activation and entry of antigen-specific CD8(+) T cells into the central nervous system is an essential step towards clearance of West Nile virus (WNV) from infected neurons. The molecular signals responsible for the directed migration of virus-specific T cells and their cellular sources are presently unknown. Here we demonstrate that in response to WNV infection, neurons secrete the chemokine CXCL10, which recruits effector T cells via the chemokine receptor CXCR3. Neutralization or a genetic deficiency of CXCL10 leads to a decrease in CXCR3(+) CD8(+) T-cell trafficking, an increase in viral burden in the brain, and enhanced morbidity and mortality. These data support a new paradigm in chemokine neurobiology, as neurons are not generally considered to generate antiviral immune responses, and CXCL10 may represent a novel neuroprotective agent in response to WNV infection in the central nervous system.