草鱼补体蛋白MBLs调节单核巨噬细胞极化的机制研究

MBL (mannose-binding lectin) is an essential component of the lectin pathway of the complement system. To date, two functional MBL isoforms (MBL-like-1 and MBL-like-2) have been identified in teleosts, while only one functional MBL found in human, suggesting there may be functional differentiation of teleost MBLs. As a pattern recognition molecule, teleost MBL played vital roles in innate immunity. Furthermore, our recent findings in grass carp indicated that MBL-like-1 and MBL-like-2 may have different regulatory roles on monocyts/macrophage (MO/MФ) polarization. This project will focus on the mechanisms underneath this phenomenon based on previous studies. To be specific, we will study the respective function of two MBLs on MO/MФ polarization, elucidate the interaction between MBLs and C1qR, the membrane receptor of MO/MФ. Last but not least, we will illustrate the signaling pathways involved, MAPK/STAT/NF-κB or their synergistic effects. Finally, our project will not only benefit for a better understanding of the evolution of the vertebrate immune system, but also provide new perspectives for the prevention of infectious diseases in aquaculture.

MBL是补体凝集素途径的重要组分。硬骨鱼类编码两种具有生物学功能的MBL样分子，而人类仅有一种MBL分子。长期以来，鱼类MBLs被认为是模式识别分子在先天免疫中起重要作用。然而，申请者新近研究发草鱼MBL-like-1和MBL-like-2在调控单核巨噬细胞（MO/MФ）极化中有不同调控效应。本项目拟在哺乳动物及申请者前期研究的基础上，首次在草鱼中探索MBLs调节MO/MФ极化的机制。本项目拟探索两种MBL样分子在MO/MФ极化过程中各自的功能、揭示MBLs与MO/MФ膜受体C1qR相互作用以及阐明MAPK和/或STAT和/或NF-κB信号通路介导MO/MФ极化的信号调节机制。通过项目实施，不仅有助于理解脊椎动物免疫系统进化，也有助于指导硬骨鱼类细菌性疾病的防治。

MBL是补体凝集素途径的重要组分。硬骨鱼类编码两种具有生物学功能的MBL样分子，而人类仅有一种MBL分子。长期以来，鱼类MBLs被认为是模式识别分子在先天免疫中起重要作用。然而，申请者新近研究发草鱼MBL-like-1和MBL-like-2在调控单核巨噬细胞（MO/MФ）极化中有不同的调控效应。本项目证实两种MBL样分子在MO/MФ极化过程中各自的功能、揭示MBLs与MO/MФ膜受体C1qR相互作用，阐明了NF-κB信号通路介导MO/MФ极化的信号调节机制。通过项目实施，不仅有助于理解脊椎动物免疫系统进化，也有助于指导硬骨鱼类细菌性疾病的防治。