柔嫩艾美耳球虫与宿主间EGFR信号通路研究

The molecular mechanism of parasite and host interactions is the basis for deciphering the pathogenic mechanisms and the development of effective vaccines and drugs. The signaling pathway of Epidermal growth factor receptor (EGFR) is important in cell growth and proliferation. However, it is still not clear whether the interference of host EGFR signaling pathway is involved in the process of parasitic invasion and survival, also parasitic disease. Eimeria tenella is an important pathogen causing serious economic losses for the poultry industry. Currently, there is no report on the role of the EGFR signaling pathway in the process of host and E. tenella interaction. We propose to study the activation of host EGFR signaling pathway by E. tenella; EGF-like and host EGFR interaction; the activation of host EGFR signaling pathway by EGF-like. We aim to clarify the signaling mechanisms of E. tenella -host interactions from the perspective of EGFR signaling pathway, which will further our understanding of the molecular mechanisms of parasite-host interactions and facilitate the designs of new vaccines.

寄生虫与宿主相互作用的分子机制是致病机制、疫苗和药物研制的分子基础。表皮生长因子受体（EGFR）信号通路是细胞中参与生长、增殖的重要信号通路。寄生虫能否利用宿主EGFR信号通路达到侵入和寄生目的，通过干扰宿主EGFR信号通路导致寄生虫病的发生？目前对寄生虫与宿主间EGFR信号通路尚缺乏认识。柔嫩艾美耳球虫是严重危害养鸡业发展的重要病原，目前该虫与宿主作用的EGFR信号通路尚未见报道。针对这一问题，拟通过柔嫩艾美耳球虫激活宿主细胞EGFR信号通路作用；EGF-like蛋白与鸡EGFR相互作用；EGF-like蛋白激活宿主细胞EGFR信号通路作用研究。以期从EGFR信号通路角度阐明该虫与宿主间的信号传递机制，对揭示寄生虫与宿主相互作用的分子机制和疫苗设计具有重要意义。

柔嫩艾美耳球虫是严重危害养鸡业发展的重要病原，目前该虫与宿主作用的EGFR信号通路尚未见报道。本项目对柔嫩艾美耳球虫激活宿主细胞EGFR信号通路作用；柔嫩艾美耳球虫EGF-like蛋白激活宿主细胞EGFR信号通路作用；柔嫩艾美耳球虫EGF-like蛋白与鸡EGFR相互作用进行了研究。结果表明柔嫩艾美耳球虫和EGF-like 蛋白均可激活细胞EGFR-MAPK信号通路；EGFR 特异性抑制剂AG1478可削弱MAPK信号通路的激活。酵母双杂交、免疫共沉淀及GST-pull down鉴定柔嫩艾美耳球虫EGF-like与鸡EGFR存在相互作用。从而阐明柔嫩艾美耳球虫入侵过程激活宿主EGFR-MAPK信号通路，并确定柔嫩艾美耳球虫与宿主细胞鸡EGFR作用。对揭示柔嫩艾美耳球虫与宿主相互作用的分子机制和疫苗药物设计具有重要意义。