MBL在白假丝酵母菌感染中对Th17/Treg细胞平衡调节作用及机制

真菌感染形势日益严峻，白假丝酵母菌是临床最常见病原真菌，深入研究白假丝酵母菌感染免疫意义重大。已证实Thl7细胞及调节性T细胞(Treg)在抗白假丝酵母菌感染免疫中至关重要，而细胞因子环境与Toll受体（TLRs）是调节Th17、Treg细胞分化及平衡的重要因素。我们发现"天然免疫的关键分子"-甘露聚糖结合凝集素（MBL）不仅能影响CD4+T细胞增殖和细胞因子分泌，还可调节TLR2和TLR4的表达，据此提出本项目。首先分析白假丝酵母菌感染者标本，揭示MBL浓度与Th17及Treg数量的相关性；进一步建立白假丝酵母菌感染的体外模型和动物模型，剖析MBL对Th17、Treg细胞亚型分化的影响；再引入MBL与TLRs的相互关系来探讨有关信号通路，阐明MBL调控Th17/Treg细胞平衡的机制。提出MBL通过调节Th17/Treg细胞平衡抗白假丝酵母菌感染新观点，为白假丝酵母菌感染防治提供新思路。

Candida albicans (C.albicans), the most common human fungal pathogen in clinic, so, it is very significant to make more in-depth studies on immune response to C.albicans as the situation of fungal infections becomes increasingly serious. It has been proved that Thl7 cells and regulatory T cells (Treg) play key roles in anti-C.albicans immune responses, and cytokine secretion and toll-like receptors (TLRs) are key factors in regulating the differeatiation and balance of T Th17 cells and Treg cells. We have found that mannan-binding lectin (MBL), the key molecule in innate immunity, can not only affect the proliferation and cytokine secretion of CD4+ T cells, but also regulate the expression of TLR2 and TLR4. Based on obove, firstly we will reveal the clinical correlation between MBL concentration and the cell numbers of Th17 cells and Treg cells through analysis of C.albicans-infected blood specimen. Furthermore, we will establish C.albicans infection models in vitro and in vivo, and analyze how MBL affect the impact the differeatiation of Th17 cells and Treg cells. In addition, we will explore the related signal pathways which regulated the relation of the interaction of MBL to TLRs, and to clarify the mechanism how MBL regulates Th17/Treg balance. We would propose a new opnion that MBL can regulate TH17/Treg balance to inhibit C.albicans infection, and provide new ideas for the prevention and treatment of C.albicans infection.