大黄鱼清道夫受体MARCO抗哈维氏弧菌感染的分子机制

Due to overfishing and environmental destruction wild resources of Larimichthys crocea decrease gradually in recent years, and its aquaculture rises and expands increasely. During breeding Vibriosis brought by Vibrio harveyi is a serious disease that cause devastating death and restrict healthy breeding and sustainable development of Larimichthys crocea. There is an urgent need to clarify the immunity and the resistance mechanism to the disease, which will provide the theoretical foundation and technical support for the aquaculture of Larimichthys crocea . As the key moleculars in natural immune system, Scavenger receptors (SR) can identify a large number of foreign antigen by recognizing conserved molecular of the pathogen. They are the important lines of defence in the body's immune defense. Therefore, based on the status of Larimichthys crocea threatened by Vibrio harveyi，the project will study MARCO in SR superfamily and its interaction mechanism with the pathogenic bacteria. In the previous studies, we had got the DNA and cDNA sequence of MARCO, and the expression of MARCO increased significantly during Vibrio harveyi infection. On the basis of earlier results the consequent study will detect the spatio-temporal expression features of MARCO and its cell positioning situation. The molecular mechanisms of bacterial identification mediated by MARCO will be ascertained and its features involved in NF-κB signal transduction will be analyzed through expression of report genes by microinjection. The results may provide the targets for drug design and also can be theoretical reference for diseases prevention and control in the economic fish.

随着大黄鱼养殖业的迅猛发展和养殖规模的不断扩大，病害问题日益凸显，其中由哈维氏弧菌引起的弧菌病尤为严重，造成养殖大黄鱼毁灭性死亡，成为制约该品种养殖健康持续发展的关键因素，因此阐明大黄鱼的免疫生物学特征和抗病机制迫在眉睫。清道夫受体A家族的MARCO基因作为天然免疫系统的关键分子，可识别大量异己抗原，是机体免疫防御的重要防线，因此，本研究立足于大黄鱼养殖过程中受到哈维氏弧菌威胁的现状，拟在获得MARCO基因DNA及cDNA序列，并检测到鱼体受哈维氏弧菌感染后，MARCO表达量迅速上调的基础上，探明该分子细胞定位情况，分析其识别病原菌的分子机制，发掘MARCO参与NF-κB信号转导的功能特征，从而确定MARCO介导宿主抗哈维氏弧菌感染的分子机制。研究结果将为大黄鱼抗病制剂研发提供药物设计方案及靶点，亦可为经济鱼类病害问题的科学防控提供理论参考。

随着大黄鱼养殖业的迅猛发展和养殖规模的不断扩大，病害问题日益凸显，其中由哈维氏弧菌引起的弧菌病尤为严重，造成养殖大黄鱼毁灭性死亡，成为制约该品种养殖健康持续发展的关键因素，因此阐明大黄鱼的免疫生物学特征和抗病机制迫在眉睫。清道夫受体A家族的MARCO基因作为天然免疫系统的关键分子，可识别大量异己抗原，是机体免疫防御的重要防线，本研究立足于大黄鱼养殖过程中受到哈维氏弧菌威胁的现状，克隆获得MARCO基因DNA及cDNA序列，分析其分子特征及进化规律，进一步通过实时荧光定量PCR技术检测发现鱼体受哈维氏弧菌感染后，MARCO表达量迅速上调；通过构建目的基因的真核表达质粒探明该分子定位于细胞膜，与LPS和病原菌存在识别和剂量效应，通过检测清道夫A家族信号通路相关成员的表达特征，发掘MARCO参与信号转导的功能特点，从而确定MARCO介导宿主抗哈维氏弧菌感染的分子机制。研究结果将为大黄鱼抗病制剂研发提供药物设计方案及靶点，亦可为经济鱼类病害问题的科学防控提供理论参考。