弓形虫新基因wx2通过SOCSs-JAKs-STATs与线粒体凋亡途径调节宿主免疫的机制研究

弓形虫是一种严重危害人类健康和畜牧业发展的机会致病寄生原虫，所致弓形虫病流行范围广，目前尚无针对缓殖子和耐药虫株的有效药物，弓形虫疫苗也尚未成功。作为最成功的的寄生虫，弓形虫在其寄生过程中逐渐演化出一系列调控宿主免疫应答的机制，以达到免疫逃避的目的。本课题组通过单克隆抗体技术、免疫筛选cDNA文库获得弓形虫新基因wx2，研究显示该分子与宿主凋亡调控相关，在弓形虫的免疫原性和致病性方面具有重要的作用。靶向敲除该基因后弓形虫毒力降低，对宿主细胞的入侵和自身繁殖能力也明显下降；小鼠攻击实验显示Th1和Th17细胞免疫应答上调；且淋巴细胞的Cis基因的表达下调，提示wx2参与了宿主免疫应答和免疫调节。我们拟进一步研究该基因调控宿主SOCSs-JAKs-STATs信号负反馈通路及凋亡参与免疫调节的分子机制，为进一步防治弓形虫病的药物研制和疫苗开发奠定理论和实践基础。

Toxoplasma gondii(T.gondii)is an opportunity parasite which cause widely prevalent of Toxoplasmosis that seriously endanger human health 、livestock and poultry. At present, there is no good method to control the bradyzoites in cyst. As the most successful parasite, T.gondii has gradually evolved a series of mechanisms that regulate the host's immune response during its parasitic process to achieve the purpose of immune evasion. Our group obtained a new gene wx2 of T.gondii by using monoclonal technology and immune screening cDNA library. In the previously researches, it was found that the protein encoded by wx2 interacted with host apoptosis regulatory proteins. The virulence and the ability to invade and reproduce in host cells has been decreased after targeted knockout of wx2. Mouse challenge experiments have shown that the immune response of Th1 and Th17 cells is up-regulated; and the expression of the Cis gene in lymphocytes has been decreased also, suggesting that wx2 involved in host immune response and immune regulation. To further study the mechanism of which regulates host signaling pathways and the role of apoptosis in immune regulation, explore the balance of resistance between T.gondii and their hosts, and lay a theoretical and practical basis for further drug development and vaccine development against Toxoplasmosis.