cGAS功能缺陷的鸡细胞中STING介导DNA免疫识别机制

STING利用DNA识别受体侦测病原并介导IFN激活是哺乳动物DNA免疫识别主要方式。我们研究确认鸡STNG参与DNA免疫识别，然而，鸡STING介导DNA免疫识别机制不清楚。进一步研究发现，DNA识别重要通路cGAS-STING-IFN在鸡中天然缺陷，使鸡DNA识别机制更加扑朔迷离。.本项目拟通过互作蛋白筛选、CRISPR文库筛选等宏观手段，结合过表达、基因敲除等细致功能学研究，挖掘鸡依赖STING的DNA识别受体（SDR）；并以DDX41等为代表，通过对其识别DNA机制、激活STING机制等研究，阐明鸡SDR依赖STING参与DNA免疫识别的信号转导机制；通过对病毒感染后SDR信号通路激活比较，探索鸡不同SDR抗DNA病毒主次关系及互作网络。成果将揭示cGAS功能缺陷的鸡细胞中STING介导DNA免疫识别独特机制，不仅为禽天然免疫学提供基础数据，而且为禽DNA病毒临床防治提供理论指导。

DNA pattern recognition receptors (DPRs) can sense cytosolic dsDNA and induce type Ⅰ interferons via a central adaptor named STING, which is the major method of DNA recognition in mammalian cells. Chicken STING was also found to be involved in the immune sensing of cytosolic dsDNA in our previous study; however, the mechanism remains unknown. Our further study showed that cGAS-STING-IFN, which is the most important DNA sensing signaling pathway in mammals, is defective in chickens. This defect makes the mechanism of DNA immune recognition in chickens more confusing. .In this project, macroscopic research methods, including nucleic acid-protein interactions and CRISPR library screening, and specific functional research, such as gene overexpression and gene knockout, will be used to explore the chSTING-dependent DPRs. With DDX41 as a representative DPR, the mechanisms of its DNA recognition and chSTING activation will be investigated to reveal the signal transduction mechanisms of the DNA immune response triggered by DPR-chSTING. Finally, both the primary and secondary relationships and the crosstalk among the identified DPRs will be preliminarily studied by comparing the activation strength of the corresponding signaling evoked by DNA viral infections. .The results will uncover the unique mechanism of DNA immune responses dependent on chSTING in cGAS-STING-IFN-defective chicken cells, which not only provides basic data for avian innate immunological research but also provides theoretical guidance for the clinical prevention and treatment of DNA viral infections in avian species.