Immunomodulatory Cytokines Determine the Outcome of Japanese Encephalitis Virus Infection in Mice
Immunomodulatory Cytokines Determine the Outcome of Japanese Encephalitis Virus Infection in Mice
复制标题
DOI：
10.1002/jmv.21688
复制
发表时间：
2010-02-01
影响因子：
12.7
通讯作者：
Ghosh, D.
中科院分区：
文献类型：
--
作者：
Biswas, S. M.;Kar, S.;Ghosh, D.
日本脑炎病毒（JEV）是一种急性中枢神经系统感染，其致病机制尚未完全清楚。为了研究宿主对JEV感染的反应，通过神经途径感染14日龄小鼠，导致脑炎和死亡。接受JEV免疫脾细胞转移的小鼠免受神经JEV感染。然后在死于JEV感染或通过JEV免疫细胞转移保护免受感染的小鼠脑中比较病理学和基因表达谱。进行性JEV感染小鼠的促炎细胞因子、趋化因子和与干扰素（IFN）通路相关的信号转导子的表达增加。相反，接受免疫细胞转移的小鼠Th 2细胞因子IL-4和IL-10的产生增加，IFN-γ的表达减弱。我们观察到IL-10是决定JEV感染临床结局的重要因素。通过微阵列分析获得的数据通过定量RT-PCR进一步证实。总之，这些数据表明，JEV感染引起不受调节的炎症反应，可以通过在致死感染后存活的小鼠中表达免疫调节细胞因子来对抗。J. Med. Virol. 82：304-310，2010. (C)2009威利-利斯公司
Japanese encephalitis virus (JEV) induces an acute infection of the central nervous system, the pathogenic mechanism of which is not fully understood. To investigate host response to JEV infection, 14-day-old mice were infected via the extraneural route, which resulted in encephalitis and death. Mice that received JEV immune splenocyte transfer were protected from extraneural JEV infection. Pathology and gene expression profiles were then compared in brains of mice that either succumbed to JEV infection or were protected from infection by JEV immune cell transfer. Mice undergoing progressive JEV infection had increased expression of proinflammatory cytokines, chemokines, and signal transducers associated with the interferon (IFN) pathway. In contrast, mice receiving immune cell transfer had increased production of the Th2 cytokine IL-4, and of IL-10, with subdued expression of IFN-gamma. We observed IL-10 to be an important factor in determining clinical outcome in JEV infection. Data obtained by microarray analysis were further confirmed by quantitative RT-PCR. Together, these data suggest that JEV infection causes an unregulated inflammatory response that can be countered by the expression of immunomodulatory cytokines in mice that survive lethal infection. J. Med. Virol. 82: 304-310, 2010. (C) 2009 Wiley-Liss, Inc.