共刺激分子Tim-1和Tim-3对肥大细胞介导的抗弓形虫感染免疫调节机制

项目名称： 共刺激分子Tim-1和Tim-3对肥大细胞介导的抗弓形虫感染免疫调节机制

项目编号： No.81471973

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 吕芳丽

作者单位： 中山大学

项目金额： 72万元

中文摘要： 弓形虫病的致病机制不祥。近年发现肥大细胞是重要的宿主防御效应细胞，但其在弓形虫感染中的作用一直被忽视。我们前期的研究结果发现：1)小鼠感染弓形虫后，脾脏及肠系膜淋巴结等组织中的肥大细胞数量显著增加且明显脱颗粒；2)采用肥大细胞脱颗粒刺激剂促进弓形虫感染小鼠肥大细胞脱颗粒，组织中炎症反应程度明显加重、虫荷显著增加；3)免疫荧光双染色显示，感染小鼠脾脏及淋巴结组织中的肥大细胞Tim-3表达阳性。已知Tim-1可增强Th2细胞的活化，Tim-3可下调Th1细胞的功能。Tim基因家族也表达于肥大细胞表面，但其在弓形虫感染中的作用未见报道。我们的中心假设是：肥大细胞参与弓形虫感染免疫，其免疫功能受Tim-1和Tim-3的调节。本课题拟采用体内外实验，验证：1)肥大细胞对弓形虫的直接作用；2)Tim-1和Tim-3对肥大细胞介导的抗弓形虫感染免疫的调节机制。研究结果将为弓形虫病的免疫防治提供理论依据。

中文关键词： 弓形虫；感染免疫；分子机制

英文摘要： The pathogenesis of toxoplasmosis remains not fully understood. In recent years, it has been reported that mast cells is an important host defense effector cells, but its role in Toxoplasma gondii infection has been neglected. Our previous study found that: 1) mice infected with T. gondii, the number of mast cells in the spleen and mesenteric lymph nodes and other tissues were significantly increased and obviously degranulated; 2) T. gondii-infected mice treated with mast cell activator, there were significantly increased tissue inflammation and significantly increased parasite burden compared with infected controls; 3) Tryptase-TIM-3 double-positive mast cells were observed in the spleen and lymph node tissues of T. gondii-infected mice by immunofluorescence staining. Tim-1 is known to enhance the activation of Th2 cells, and Tim-3 is to reduce function of Th1 cells. Tim gene family is also expressed on the surface of mast cell, but their role in T. gondii infection has not been reported. Our central hypothesis is: mast cells involve in the infective immunity of T. gondii infection, their immune function is regulated by Tim-1 and Tim-3 genes. This project intends to use in vivo and in vitro models to test: 1) the direct effect of mast cells against T. gondii; 2) the immune regulatory mechanism of Tim-1 and Tim-3 on mast cell-mediated immunity to T. gondii infection. The results will provide a theoretical basis for immune prevention and treatment of toxoplasmosis.

英文关键词： Toxoplasma gondii;infective immunity;molecular mechanisim