乙肝病毒（HBV）持续感染会使机体产生针对HBV抗原的免疫耐受，导致慢性感染而不能产生特异的细胞免疫反应。HBV DNA疫苗能刺激机体产生特异性免疫反应，已被用于慢性HBV感染治疗的研究，但效果不理想。侧耳凝集素（POL）是从侧耳（平菇）中纯化的一种天然活性蛋白，申请人研究首次发现（Vaccine, 2013）POL提高了HBV DNA疫苗免疫原性，激发免疫耐受小鼠HBV抗原特异性免疫反应，但其作用机制尚不清楚。初步结果提示POL上调DCs表达套样受体6（TLR6），推测POL可能通过TLR6激活DCs发挥作用。本项目在前期结果基础上，结合最新进展拟分析POL作用于DC的上TLR6受体及其下游信号通路，揭示POL激活DCs的作用；再利用基因敲除及信号分子抑制剂验证POL激活DCs在打破HBV抗原免疫耐受中的功能。本研究将为HBV慢性感染治疗提供新的思路，并为食用菌凝集素的研究提供参考。

Hepatitis B virus (HBV) continous infection can cause immune tolerance to HBV antigen and and become chronic infection, so the specific cellular immune response can not be induced. HBV DNA vaccine can elicit specific immune response and has been used for chronic HBV infection treatment, but the effect is not ideal. Pleurotus ostreatus lectin (POL) purified from Pleurotus ostreatus is an natural and active protein. Our previous study firstly demonstrated that POL enhanced the immunogenicity of HBV DNA vaccine and stimulated HBV antigen specific immune responses in immune tolerance mice, but the mechanism is not clear. The preliminary data indicated that POL upregulated TLR6 expression of DCs, so we speculated that POL may bind TLR6 for DCs activation. On the basis of preliminary results, this study will analyze TLR6 and the downstream signal pathway of DCs stimulatied by POL which will reveal the stimulation function of DCs by POL. To verify the function of DCs activated by POL for breaking HBV antigen immune tolerance, the gene knochout mice and inhibitors of signal molecules will be used. These study could provide not only new ideas for chronic HBV infection therapy, but also informations for mushroom lectins research.

乙肝病毒（HBV）持续感染会使机体产生针对乙肝抗原的免疫耐受，导致慢性感染而不能产生特异的细胞免疫反应。HBV DNA疫苗能刺激机体产生细胞免疫反应，但免疫效果不太理想。侧耳凝集素（POL）是从侧耳（平菇）中纯化的一种天然活性蛋白，我们前期研究首次发现POL能够提高了HBV DNA的免疫原性，但其作用机制尚不清楚。本项目在前期结果基础上发现POL能够激活树突细胞（DCs），刺激炎性因子IL-6和TNF-α的产生，并通过DCs上的套样受体6（TLR6）激活接头分子MyD88及NF-κB信号通路，进而激活细胞免疫反应。本项目的研究结果首次发现POL激活TLR6介导的NF-κB信号通路，为HBV慢性感染治疗提供了新的思路，并为食用菌凝集素的研究提供参考。