鸡滑液支原体分泌蛋白MSLP53调控NF-κB信号通路发挥致病作用的分子机制

Mycoplasma synoviae (MS) infection is one of the most important diseases to the world poultry industry, and recently it becomes more and more serious in China. So far, we know little about the virulent factors of MS, which impeding the improvement of the MS prevention and control research. Secreted proteins play important roles in the pathogenesis of virulent bacteria. Previously we found that the secreted protein MSLP53 of MS can promote the up-regulation of inflammatory cytokines in the host cells. This study was aimed to detect the effect of MSLP53 on the NF-κB signaling pathway in host cells, screen and identify the host cell proteins interacted with MSLP53, analyze the molecular mechanism of MSLP53 regulating NF-κB signaling pathway. Meanwhile, we try to construct MSLP53 mutant MS strain, and to study its effect on the pathogenicity of MS. At last， we try to further elucidate the molecular mechanism of the secreted protein MSLP53 regulating the NF-κB signaling pathway to play roles in pathogenesis of MS. This project will not only help us better understanding of the pathogenesis of MS, but also provide a theoretical basis for the development of new treatment strategies and vaccine developments.

滑液支原体（MS）感染是危害世界养禽业不容忽视的重要疾病，近几年在我国有加重趋势。目前关于MS致病因子知之甚少，严重阻碍防控研究的进展。分泌蛋白在病原菌致病过程中有重要作用，申请人前期研究发现，MS的分泌蛋白MSLP53能促进宿主的炎性细胞因子显著上调表达。本研究拟通过检测分泌蛋白MSLP53对宿主细胞NF-κB信号通路的影响，筛选并鉴定MSLP53的宿主细胞互作蛋白，分析MSLP53调控NF-κB信号通路的分子机制；同时构建MS的MSLP53突变株，研究其对MS致病力的影响；进一步阐明分泌蛋白MSLP53调控NF-κB信号通路发挥致病作用的分子机制。本项目的开展不仅有助于加深对MS分子致病机制的了解，还可为发展新的治疗策略和疫苗开发提供理论基础。

近几年滑液支原体(MS)在我国发病情况日趋严重，越来越受到大家的广泛关注。对MS分泌蛋白在致病机制方面的研究有助于发展新的诊疗策略。本项目成功鉴定到MS的分泌蛋白MSLP53，证明MSLP53不仅能黏附、内化进入宿主细胞，还能诱导宿主细胞的炎性反应，导致宿主细胞凋亡。经P53入核试验和双荧光素酶报告试验证实，MSLP53能激活宿主细胞的NF-κB信号通路，进一步研究发现，MSLP53蛋白激活NF-κB是由TLR2介导的。MSLP53抗血清对MS黏附、侵袭以及激活宿主细胞NF-κB信号通路存在显著性抑制作用，证实了LP53蛋白在MS致病过程中发挥重要作用。此外，我们发现MSLP53蛋白是一个非常有潜力的MS诊断抗原靶标，目前已基于该蛋白建立了MS血清抗体ELISA检测方法，相关试剂盒产品正在研发中。