尼罗罗非鱼寡聚体MBL的功能解析及其调控巨噬细胞吞噬的分子机制

甘露糖结合凝集素（Mannose-binding lectin，MBL）作为先天免疫系统的关键分子，在机体防御病原菌感染中发挥重要作用。目前硬骨鱼MBL的结构特征和参与机体防御的途径及相关免疫机制，尚不明确。申请人的早期研究证实罗非鱼MBL具有模式识别、凝集和抑菌功能，并在非特异性细胞防御中发挥重要作用。鉴于此，本项目以尼罗罗非鱼为研究模型，从MBL的寡聚体结构切入，通过三个相辅相成的内容展开研究：（1）不同寡聚体MBL的分离鉴定及其功能分析；（2）寡聚体MBL启动补体凝集素途径的激活机制；（3）寡聚体MBL以一种非依赖凝集素途径的方式调控吞噬的分子机制。率先为MBL发挥进化保守功能，从而促进早期脊椎动物调理巨噬细胞吞噬病菌的反应机制提供直接证据。本项目可望取得突破性的创新成果，有助于阐释硬骨鱼MBL参与机体防御病菌侵染的作用机制和完善其参与免疫应答的基础理论体系，具有重要的科学意义。

As a key molecule of innate immune system, mannose-binding lectin (MBL) plays an important role in body defense of pathogen infection. At present, the structural characteristics of teleost fish MBL and the pathways involved in body defense and related immune mechanisms are still unclear. Previous studies have found that MBL has the functions of pattern recognition, agglutination and bacteriostasis, and plays an important role in non-specific cell defense. In this project, we use Nile tilapia (Oreochromis niloticus) as the research model, starting from the MBL polymer structure, and expand through three complementary research contents: (1) separation, identification and functional analysis of different oligomer MBL; (2) the activation mechanism of oligomer MBL initiating the complement lectin pathway; (3) oligomer MBL regulating the molecular mechanism of macrophages phagocytosis in a lectin-independent manner. These results provide the first evidence on the response mechanism of MBL performing evolutionary conserved function to promote opsonophagocytosis of macrophages in early vertebrates. This project is expected to achieve breakthrough and innovative results, which will help to explain the mechanism of bony fish MBL in the defense against pathogen infection and improve the basic theoretical system of its participation in immune response, with great significance in science.