Tim-3/Galectin-9介导免疫细胞异常在布鲁氏菌免疫逃避中的作用研究

Brucellosis is a serious zoonosis in Xinjiang. The lack of knowledge of the pathogenesis of brucellosis hinders the effective prevention and control. Tim-3/Galectin-9 plays an important role in the immune evasion of pathogens. But its role in brucellosis is not clear. Our Preview study show that Tim-3/Galectin-9 was involved in the immune evasion of Brucella. However, the mechanism is not clear. Based on the immune evasion mediated by Tim-3/Galectin-9 molecule in brucellosis patients and infected mice, the activation of Tim-3/Galectin-9 pathway in brucellosis patients and infected mice before and after treatment was studied, in order to clarified the relationship between Tim-3/Galectin-9 pathway and brucellosis. we analyze the the negative regulatory effect of Tim-3/Galectin-9 pathway on the functional activity of macrophages and T cells by blocking the Tim-3/Galectin-9 pathway， to elucidate the role of host immunosuppressive state formation and maintenance, Regulation of Tim-3/Galectin-9 Pathway by Wild Brucella on macrophages and T cells were studied in order to clarified the relationship between brucella infection and host immunity, which provided a new idea for the study of the prevention and treatment of Bruce's disease, which was aimed at blocking immune escape signal pathway.

布鲁氏菌病是新疆地区严重的人畜共患病，对其发病机制认识不足阻碍了有效的防治研究。Tim-3/Galectin-9在病原体的免疫逃避中发挥了重要作用，但其在布鲁氏菌病中的作用尚未明确。我们前期发现，Tim-3/Galectin-9也参与了布鲁氏菌的免疫逃避，但其机制尚不清楚。本项目从布鲁氏菌病患者和感染小鼠Tim-3/Galectin-9分子介导的免疫逃避为切入点，研究治疗前后布鲁氏菌病患者和感染小鼠Tim-3/Galectin-9通路的激活，明确其与布鲁氏菌病关系。通过阻断Tim-3/Galectin-9通路，分析Tim-3/Galectin-9通路对巨噬细胞和T细胞功能活性的负调控作用，阐明宿主免疫抑制状态形成和维持上所起的作用。用野生布鲁氏菌调节Tim-3/Galectin-9通路对巨噬细胞和T细胞影响，阐明布鲁氏菌感染与宿主免疫的关系，为开展以阻断免疫逃避信号途径为靶点的布鲁斯菌病防

布鲁氏菌病是由布鲁氏菌(Brucella，Bru)感染引起的一种严重人兽共患传染病，其危害巨大，能累及人体多个脏器，一旦转为慢性阶段，将很难治愈，但是目前布鲁氏菌病发病机制还不明确。基于 Tim-3/Galectin-9抑制免疫应答导致病原体免疫逃避成为研究感染性疾病慢性化的热点。本研究将Tim-3/Galectin-9 介导免疫耐受的机制引入到布鲁氏菌病领域研究，从患者，体外和动物三个层面，研究Tim-3/Galectin-9 在布鲁氏菌病中的作用机制，研究发现Tim-3在CD4+T细胞表达水平升高，其Th1,Th2,Th17,Treg上Tim-3表达均增高，在疾病的不同进展阶段，慢性期布鲁氏菌病患者CD4+T细胞及其亚群Th1,Th2,Th17,Treg上Tim-3水平高于急性期，均高于正常组。Tim-3的表达与Th1,Th2,Th17分泌细胞因子水平呈负相关，与Treg细胞因子呈正相关。体外活化和阻断Tim-3/Galectin-9通路，发现Tim-3/Galectin-9通路调控CD4+T细胞及其亚群的功能。研究结果极大的丰富 Tim-3/Galectin-9调控免疫应答在布鲁氏菌致病机制说起的作用，为布鲁氏菌病治疗提供新的研究领域。同时也会对布鲁氏菌病的慢性化的致病机制有一个新的认识。为防止布鲁氏菌病慢性化，临床干预提供理论基础。