胶质细胞在猪血凝性脑脊髓炎病毒感染CNS中的免疫应答机制

项目名称： 胶质细胞在猪血凝性脑脊髓炎病毒感染CNS中的免疫应答机制

项目编号： No.31472194

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 水产学、兽医学

项目作者： 贺文琦

作者单位： 吉林大学

项目金额： 87万元

中文摘要： 在中枢神经系统（CNS）损伤诱发的自身先天性免疫应答中，小胶质细胞和星形胶质细胞发挥重要作用。猪血凝性脑脊髓炎病毒（PHEV）具有典型的嗜神经性，主要侵害CNS导致感染动物死亡。在PHEV感染过程中，这些胶质细胞参与的神经免疫与抗PHEV感染和病毒致脑损伤之间的关系目前尚不清楚。本项目拟以小胶质细胞和星形胶质细胞为研究对象，开展PHEV感染小鼠脑组织中胶质细胞的激活状态及其分泌细胞因子、趋化因子及Ⅰ型干扰素信号的免疫应答研究；应用体外培养的原代胶质细胞，进行重要炎症介质和干扰素信号通路相关基因的检测，结合体内试验结果，分析其在神经免疫和神经病理损伤中的作用；进而以体外建立的小鼠脑活组织培养模型进行PHEV感染，明确炎性细胞浸润对该病毒所致神经炎症的影响程度。预期结果不仅可以系统地阐明胶质细胞在PHEV感染CNS中的免疫应答机制，而且为深入解析PHEV的致病机制奠定基础。

中文关键词： 血凝性脑脊髓炎病毒；神经损伤；天然免疫；胶质细胞；Ⅰ型干扰素

英文摘要： Gila are key players of the immune response in the central nervous system (CNS) and, being the resident innate immune cells, they are responsible for the early control of infections. Porcine hemagglutinating encephalomyelitis virus (PHEV) mainly invades the CNS of host, and the brain injury with nonsuppurative encephalomyelitis caused by PHEV is an important reason for acute death of infected host. Although the glia's immune resoponses in the CNS during PHEV infection remains poorly understood, we speculate that it should be the host's first line of defense against invading PHEV. Based on this hypothesis, PHEV infection of the BALB/c mice, the primary cultured glia (microglia and astrocytes) and live brain tissue slices from 2-3 day old mice were used as in vivo, in vitro and ex vitro model system, respectively, to investigate innate immune responses during PHEV's encephalitis, including the activation of glia (microglia and astrocytes) and type I interferon signaling and increased expression of inflammatory mediators in this study. The activation of glia will be evidenced by characteristic changes in cellular morphology and expression of astrocyte and microglia-specific proteins.Expression of inflammatory mediators known to be released by activated glia and genes involved in IFN signaling will be detected using the genetic chip, real-time PCR, ELISA, western boltting assays, etc. The prospective results will be helpful to understand deeply the roles of innate immune responses in the CNS during PHEV infection, and the relationship between the neuroinflammation and brain damage caused by PHEV infection.In addition, PHEV infection of the CNS will provide a model for understanding the basic pathogenic mechanisms of virus-induced CNS injury.

英文关键词： Hemagglutinating encephalomyelitis virus;neurologic damage;innate immune response;glia;Type Ⅰ IFN