基于定向选择系的微进化解析鸡异嗜性粒细胞的抗菌机制

异嗜性粒细胞（Heterophil，H）是禽类特有的免疫细胞，通过精确调控来识别和杀灭病原微生物。在团队前期研究中，建立的异嗜性粒细胞与淋巴细胞比值为主选性状的选择系已开展了12个世代的选育，通过沙门氏菌感染试验，初步证实选择系的H细胞的吞噬、脱粒和氧化爆发等功能强弱是抗菌能力差异的内在因素，但引起这些功能的分子调控机制还远未解析。本研究在对该定向选择系的不同世代基因组重测序和微进化分析的基础上，在人工感染沙门氏菌的条件下通过比较中外鸡种的抗菌差异、H细胞转录组差异，筛选参与调控H细胞吞噬、脱粒等抗菌功能的通路和基因，并重点分析H细胞上跨膜信号通路（FcR）和上游基因（PTPRJ）的作用机制；对具有重要效应的关键基因利用CRISPRi干扰实验以及多品种基因频率进一步确认，最终解析出鸡特有异嗜性粒细胞抗菌功能的信号通路和分子机制。本研究将为鸡抗病育种提供理论依据。

Heterophil refers to the white blood cell characterized by the function of phagocytosis and killing in the avian immune system, which can identify and kill pathogenic microorganisms by precise regulatory mechanisms. We have established heterophil/lymphocyte ratio (H/L) selection strain, which had been carried out for 12 generations. Salmonella infection assay showed that the mortality rate of the selective strain was lower than the control strain, which was preliminarily proved that the phagocytosis, cell threshing and oxidative explosion of the selected heterophil underlying the difference in antibacterial ability, but the regulatory mechanisms were far from solved. This study aims to firstly analyze difference of anti-bacteria ability of foreign and indigenous chicken breeds, analyze the transcriptomes of heterophil from selection lines and get the candidate genes involved in the regulation of heterophil function. After that, we will analyze how the transmembrane pathway (FcR) and the upstream gene (PTPRJ) affect the function of heterophil. In addition, we will apply CRISPRi interference to decipher the function of key genes, as well as analyze the signal pathway and molecular mechanism of the antibacterial function of heterophil. This study will offer theoretical basis for disease resistance breeding of chicken.