弓形虫表面抗原SAG1互作蛋白筛选及调控虫株入侵、宿主细胞免疫的机制研究

刚地弓形虫是重要的人兽共患原虫，其依赖虫株表面抗原SAG1（TgSAG1）粘附宿主细胞，而后TgSAG1调控虫株分泌细胞器分泌入侵相关蛋白启动虫株入侵；TgSAG1抗原表位被封闭后，虫株的宿主细胞粘附率、入侵率均显著降低。前期我们鉴定了与RH-WT株相比，RH-∆sag1株的差异表达基因及虫株感染过程中TgSAG1宿主及虫株互作蛋白质组，提示TgSAG1在虫株粘附与感染细胞过程中发挥重要作用。综合以上研究背景我们提出：TgSAG1结合宿主细胞膜蛋白使虫株粘附于宿主细胞，而后TgSAG1调节其下游基因表达或直接结合虫株入侵相关蛋白启动虫株入侵过程；TgSAG1作为强免疫原，依赖宿主蛋白调节宿主免疫。本研究以虫株与宿主为研究对象，阐明TgSAG1调控虫株粘附、入侵及诱导宿主免疫的作用机制，为开发抑制虫株入侵的特异性小分子抑制剂及疫苗研究提供理论基础，对抑制或预防虫株感染具有重要意义。

Toxoplasma gondii (T. gondii) is an important zoonotic protozoan. It depends on the surface antigen 1 (TgSAG1) for attaching to the infected cells, then TgSAG1 regulate the secretory organelle to secrete invasion related proteins and initiate the T. gondii invasion. when the TgSAG1 epitope blocked, the attachment and invasion rate of T. gondii are significantly decreased. We identified the Differential expression genes (DEGs) in RH-∆sag1 strain compared with RH-WT strain. Meanwhile, TgSAG1 interacting proteome of hosts and parasites were screened out, which clarified the importance of TgSAG1 in regulation of the parasite’s invasion. According to the results we obtained, we propose that: TgSAG1 binds to the host cell membrane protein for T. gondii attach to the host cell, then TgSAG1 initiate the parasite invasion by regulating its downstream genes expression or bind with invasion related proteins. In addition, as an immunogen, TgSAG1 could stimulates the host's immunity by binding to the host protein. In this study, we intend to explore the mechanism of TgSAG1 regulating the attachment, invasion of T. gondii and inducing host immune response from the perspective of T. gondii and host, to provide a theoretical basis for the development of specific small molecule inhibitors and vaccine development against T. gondii invasion, which is of great significance for inhibiting or preventing the infection of T. gondii.