布鲁氏菌在巨噬细胞内生存增殖造成慢性感染，必须逃避不同阶段的宿主免疫反应。在布鲁氏菌先天性免疫中，与布鲁氏菌互作的蛋白和信号传导分子在布鲁氏菌免疫逃逸中起着非常重要的作用。Nrdp1和SOCS-1是免疫相关的E3泛素酶，具有调控宿主TLR的信号转导作用。本项目拟通过：① 采用酵母双杂交、免疫共沉淀及GST-pull down技术来筛选验证与Nrdp1、SOCS-1互作的布鲁氏菌效应蛋白；② 构建布鲁氏菌效应蛋白缺失株，在细胞水平研究布鲁氏菌效应蛋白对巨噬细胞E3泛素酶、TLR信号转导的调节作用；③感染小鼠，检测对小鼠TLR信号转导的调节作用。本研究对揭示布鲁氏菌调节宿主免疫反应的规律有重要意义，为阐明布鲁氏菌胞内存活机制奠定基础，为布鲁氏菌病的防控提供科学依据。

Brucella have to avoid different stage host immune response to living in macrophage. In innate immune response to Brucella, the Brucella effect proteins interaction with signals of host are important to avoid from innate immunity system. Nrdp1 and SOCS-1 are E3 ubiquitins which could control the signal transport from TLR. We dicide, first identify the effect proteins from brucella which could interact with Nrdp1 or SOCS-1,second knock out the effect gene from Brucella, then infect mouse macrophage RAW264.7 with the Brucella without effect gene, comparise with with it in the TLR signal way, third infect mouse ,comparise the TLR sgnal way..The study is important to discribe Brucella controling the host immune response,the machanism of Brucella living in cells and take some clues for Brucellosis control.