泡型包虫病（AE）是泡球蚴（Em）寄生肝脏所致“类肝癌样”致死性寄生虫病，Em诱导的免疫耐受机制未见报道。我们前期研究发现，Em感染后诱导宿主肝脏TGF-β1高表达，而NK细胞的比例明显降低，两者呈现出负相关性，提示TGF-β1可能通过诱导NK细胞耗竭造成Em免疫逃逸，但机制不明。本项目拟通过体外培养NK细胞，添加hTGF-β1细胞因子刺激或TGF-β1中和抗体，明确TGF-β1对NK细胞表型、细胞周期和功能的影响；其次建立Em感染小鼠模型，采用反向细胞清除和正向过继转输方式，明确肝脏NK/NKT细胞天然免疫应答在泡球蚴感染所致免疫耐受过程中的关键作用及其分子机制。利用临床AE肝脏手术标本和外周血，确定NK细胞的功能变化和临床表现，明确TGF-β1介导泡球蚴感染所致肝脏NK细胞免疫耐受机制及其阻断对AE病人的临床治疗的可行性，对深化AE致病机制的研究和探讨新的免疫治疗策略具有重要科学意义。

Alveolar echinococcosis (AE) is characterized by the tumor-like growth of Echinococcus multicularis (Em). Very little is known about the immune tolerance mechanism induced by Em infection. In our previous study, we found that the host liver TGF-β1 expression increased after Em infection, whereas the percentage of NK cells decreased significantly. The inverse correlation between TGF-β1 and proportion of NK cells, suggest that Em immune escospe may be caused by TGF-β1 inducing NK cells exhaustion, of which mechanism, very little is known to date. The aim of this work or project is to cultivate NK cells by in vitro, and clear effect TGF-β1 on NK cell phenotype, cell cycle and function by adding the hTGF-β1 cytokines or TGF-β1 neutralizing antibodies; Secondly, establishing a Em infection mice model, we elucidate the key role in immune tolerance and its molecular mechanism of liver NK/NKT cells innate immune response in Em infection by way of reverse cell clearance and forward adoptive transfer. Finally, using clinical AE operation on liver specimens and peripheral blood, we would clarify the functional changes of NK cells and the clinical manifestations, which reveal the liver immune tolerance mechanism of NK cell mediated by TGF-β1 in AE patients, and the feasibility of AE patients clinical treatment by blocking-up. These results will have important scientific significance for deepening the study of the pathogenic mechanism and exploring the new immunotherapeutic strategies of AE.