项目名称： H9N2亚型禽流感病毒诱发树突状细胞功能调变的作用及其机制研究

项目编号： No.31502100

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 水产学、兽医学

项目作者： 刘青涛

作者单位： 江苏省农业科学院

项目金额： 21万元

中文摘要： H9N2禽流感病毒（H9N2 AIVs）可诱发鸡的免疫抑制近而导致疫苗免疫失败，但是H9N2 AIVs的免疫抑制机理目前仍不清楚。树突状细胞（DCs）在调控宿主的免疫应答中起关键作用，其功能的调变与包括人A型流感病毒在内的多种病毒诱发的免疫抑制相关。然而，H9N2 AIVs诱发的DCs功能调变及其机制鲜见报道。本项目拟以鸡骨髓DCs为模型，首先通过细胞因子、细胞表型、T细胞活化能力、吞噬能力等方面研究H9N2 AIVs对DCs功能的调变作用；然后通过基因芯片、qRT-PCR和RNA干扰等技术，研究DCs功能调变的分子基础；最后以鸡为模型，采用流式细胞术和过继输回等技术研究DCs在H9N2 AIVs抑制疫苗免疫应答中的作用。本项目的研究结果将有助于阐明H9N2 AIVs的免疫抑制机理，并为新型疫苗和佐剂的开发奠定理论基础，对当前的疫病防控具有重要的指导意义。

中文关键词： 家禽；致病机理；免疫抑制；与宿主相互作用；组学

英文摘要： H9N2 avian influenza viruses (AIVs) have been circulating worldwide in multiple avian species and endemic in poultry populations in china, which could cause immunosuppression in chickens and result in vaccination failure. However, the mechanisms of immunosuppression induced by H9N2 AIVs are poorly understood. DCs play a critical role in modulation host immune responses, and many viruses, including human influenza A virus, also induce host immunosuppression by dysregulating DCs functions. However, research on the strategies and mechanisms for dysregulation of DCs functions caused by H9N2 AIVs is lacing. In this work, employing chicken bone marrow-derived DCs, we will investigate the influence of H9N2 AIVs infection on DCs functions by cytokines and phenotypic changes, T-cell stimulatory capacity and engulfment capability. Furthermore, gene microarray, qRT-PCR, and RNAi tests will be performed to determine the molecular mechanisms of dysregulation of DCs functions caused by H9N2 AIVs. Finally, chicken models will be established, and flow cytometry and adoptive infusion of DCs will be performed to investigate the role of DCs in vaccination failure caused by H9N2 AIVs. These observations will provide helpful insights into the mechanisms of immunosuppression caused by H9N2 AIVs, and contribute to the development of novel vaccine and adjuvant,which will have an important guiding significance on the current clinical disease prevention.

英文关键词： poultry;pathogenesis;immunosupression;interaction with host;omics