泡球蚴感染所致肝细胞表面CD155分子的活化机制及其靶向干预研究

泡型包虫病是泡球蚴感染宿主“类肝癌样”人畜共患病，西北高发，可通过造成宿主免疫耐受而长期寄生。我们前期研究发现泡球蚴感染宿主肝脏表面CD155分子和ERK信号通路高表达并伴有T细胞耗竭，推测CD155是泡球蚴逃逸肝脏区域免疫应答的关键因子，但其活化的分子机制不明，据此提出“泡球蚴感染激活宿主肝细胞TLR4-ERK1/2-CD155途径，活化CD155分子逃避宿主肝脏免疫应答”科学假说，本课题拟研究：1.泡球蚴蛋白Em18/EpC1对肝细胞CD155分子通路的激活调控机制；2.CD155分子在泡球蚴感染小鼠中的活化机制及其对效应性CD8+T细胞耗竭调控作用；3.靶向干预肝细胞CD155活化途径关键分子对逆转泡球蚴感染所致CD8+T细胞耗竭的效能及其机制。本研究可揭示宿主肝脏表面CD155分子活化在泡球蚴感染所致免疫耐受中的分子调控机制，为探索免疫治疗包虫病奠定基础。

Echinococcus multilocularis (Em) can achieve long-term parasitic effects by causing host immune tolerance. In our previous study, we found that TIGIT’s ligand CD155 on the liver cell surface was highly expressed, which companied with T cell exhaust. It suggested that CD155 is a key molecular, which makes Em escaping the host immune response in liver microenvironment. Based on our scientific hypothesis “Em escaping from host liver immune response through TLR4-ERK1/2-CD155 activation pathway in infected host”, we planned to study: 1. The Em18/EpC1 proteins stimulation role on CD155 pathway activation in hepatocytes in vitro; 2. The CD155 pathway activation role on CD8+ T cell exhaustion; 3. The effect of anti-CD155 activation pathway on reversing CD8+ T cell exhaustion and immune tolerance in Em infected host. This study can reveal the molecular regulation mechanism of liver CD155 activation pathwayon immune tolerance state in Em infected host, so as to provide a basis forfurther exploration of immunotherapy on echinococcosis.