Chemokine receptor CCR5 promotes leukocyte trafficking to the brain and survival in West Nile virus infection.
Chemokine receptor CCR5 promotes leukocyte trafficking to the brain and survival in West Nile virus infection.
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DOI：
10.1084/jem.20042530
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发表时间：
2005-10-17
期刊：
影响因子：
--
通讯作者：
Murphy PM
中科院分区：
文献类型：
--
作者：
Glass WG;Lim JK;Cholera R;Pletnev AG;Gao JL;Murphy PM
西尼罗河病毒（WNV）感染的分子免疫发病机制知之甚少。在这里，我们描述了一个小鼠模型的特点，西尼罗河病毒使用皮下感染途径，并描绘白细胞亚群和免疫调节因子存在于大脑中的感染小鼠。WNV显著上调了趋化因子受体CCR 5及其配体CCL 5的中枢神经系统（CNS）表达，这与表达受体的CD 4+和CD 8 + T细胞、NK 1.1+细胞和巨噬细胞的CNS浸润有关。CCR 5在发病机制中的重要性是通过死亡率研究确定的，在这些研究中，CCR 5 −/−小鼠的感染是迅速和一致致命的。在大脑中，与WNV感染的CCR 5 +/+小鼠相比，WNV感染的CCR 5 −/−小鼠的病毒负荷增加，但NK1.1+细胞，巨噬细胞以及CD 4+和CD 8 + T细胞显着减少。与将WNV感染的CCR 5 +/+小鼠的脾细胞转移到感染的CCR 5 −/−小鼠中相比，将WNV感染的CCR 5 +/+小鼠的脾细胞连续转移到感染的CCR 5 −/−小鼠中增加了CNS中的白细胞积聚，并将存活率提高到60%，与感染的CCR 5 +/+对照小鼠相同。我们的结论是，CCR 5是一个重要的抗病毒和生存的决定因素，在西尼罗河病毒感染的小鼠，通过调节白细胞贩运到受感染的大脑。
The molecular immunopathogenesis of West Nile virus (WNV) infection is poorly understood. Here, we characterize a mouse model for WNV using a subcutaneous route of infection and delineate leukocyte subsets and immunoregulatory factors present in the brains of infected mice. Central nervous system (CNS) expression of the chemokine receptor CCR5 and its ligand CCL5 was prominently up-regulated by WNV, and this was associated with CNS infiltration of CD4+ and CD8+ T cells, NK1.1+ cells and macrophages expressing the receptor. The significance of CCR5 in pathogenesis was established by mortality studies in which infection of CCR5−/− mice was rapidly and uniformly fatal. In the brain, WNV-infected CCR5−/− mice had increased viral burden but markedly reduced NK1.1+ cells, macrophages, and CD4+ and CD8+ T cells compared with WNV-infected CCR5+/+ mice. Adoptive transfer of splenocytes from WNV-infected CCR5+/+ mice into infected CCR5−/− mice increased leukocyte accumulation in the CNS compared with transfer of splenocytes from infected CCR5−/− mice into infected CCR5−/− mice, and increased survival to 60%, the same as in infected CCR5+/+ control mice. We conclude that CCR5 is a critical antiviral and survival determinant in WNV infection of mice that acts by regulating trafficking of leukocytes to the infected brain.
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影响因子：
3.7
作者：
Glass WG;Liu MT;Kuziel WA;Lane TE
通讯作者：
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影响因子：
168.9
作者：
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DOI：
10.1016/s0749-0739(17)30087-1
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