TSLP联结角膜真菌感染天然免疫与获得性免疫的机制

项目名称： TSLP联结角膜真菌感染天然免疫与获得性免疫的机制

项目编号： No.81470604

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： 吴欣怡

作者单位： 山东大学

项目金额： 73万元

中文摘要： 真菌性角膜炎是最严重的致盲性眼病之一，从天然免疫和获得性免疫的双重角度全面揭示角膜抗真菌免疫防御机制是防治角膜真菌感染的关键。我们已经率先证实TLRs是角膜真菌感染早期天然免疫的关键受体，获得性免疫可能参与感染中晚期过程，二者协同清除真菌。目前尚未见有关角膜抗真菌天然免疫与获得性免疫相互联系的研究报道。近年获得性免疫组分TSLP的功能研究揭示真菌刺激人呼吸道上皮细胞高表达TSLP，过敏性疾病中TLRs调控TSLP的表达。我们初步试验发现TSLP参与角膜抗真菌免疫过程并与TLRs密切相关。本课题拟体外实验及动物模型进一步证实TSLP增强角膜真菌感染早期TLRs介导天然免疫、参与启动感染中晚期获得性免疫，提高角膜抗真菌感染的免疫防御能力，促进炎症消退。明确TSLP作为桥梁和纽带联结角膜真菌感染天然免疫与获得性免疫的作用及机制，为更全面的研究角膜抗真菌免疫防御体系及抗真菌感染新药的研发提供靶点。

中文关键词： 真菌性角膜炎；TSLP；天然免疫；获得性免疫；Toll样受体

英文摘要： Fungal keratitis is among the most serious vision-threatening ocular infections. Clarification of the mechanism of corneal fungal infection from the viewpoint of both innate and acquired immunity is the key to treatment and prevention of fungal keratitis. We innovatively demonstrated that TLRs played essential roles in early corneal antifungal innate immunity. At the same time acquired immunity was found to be participated in the process of mid-late corneal immune response to fungal invasion. Innate and acquired immunity cooperate to eliminate fungal pathogens. At present, no research on the intercommunication of innate and acquired immunity in fungal keratitis has been reported. Recent functional studies on acquired-immunity component TSLP have suggested that TSLP was potently induced when human bronchial epithelial cells were exposed to fungi, and TLRs could modulate the expression of TSLP in allergic diseases. Our preliminary studies found that TSLP involved in the process of corneal antifungal immune response, which was closely related to TLRs. In the present project, we intended to further confirm that TSLP could strengthen the early innate immunity mediated by TLRs and participate in the initiation of mid-late acquired immunity in antifungal defensive response, which enhance corneal defense against invading fungi and accelerate inflammation subsiding. A clear understanding of the mechanisms for TSLP bridging the innate and acquired immunity in fungal keratitis is required to more comprehensively investigate the system of corneal immune response to fungal invasion and provide targets for new antifungal pharmaceuticals.

英文关键词： fungal keratitis;TSLP;innate immunity;acquired immunity;TLRs