病毒性睾丸炎是引起男性不育的重要病因。睾丸是典型的免疫豁免器官，容易受到多种病原体的感染，为了有效抵御病原体，睾丸建立了局部天然免疫防御机制。但某些病毒感染可破坏睾丸免疫稳态，从而导致睾丸炎，睾丸免疫环境的调节机理是生殖免疫学领域广泛关注的重要科学问题。本项目拟利用RNA病毒和DNA病毒感染的小鼠睾丸炎模型，系统研究RNA/DNA感受器介导的睾丸天然免疫反应与睾丸炎的关系、及其对精子发生的影响。主要内容包括：（1）通过配体激活或病毒感染，研究睾丸天然免疫反应与睾丸炎的关系；（2）利用RNAi技术和敲除小鼠模型，研究RNA/DNA感受器介导睾丸细胞天然免疫反应的分子机制。目的是揭示病毒感染诱导睾丸炎及导致雄性不育的机制，认识关键调控环节，为防治相关疾病提供干预靶点。项目拟培养研究生2-3人，在领域内主流SCI杂志上发表论文2篇。

Viral orchitis is one of the major etiological factors of male infertility. The mammalian testis is a remarkable immunoprivileged organ, which may be infected by various pathogens. The testis adopts effective local innate defense system against microbial infections. However, various virus infections would disrupt the testicular immune homeostasis, resulting in orchitis and male infertility. Thus, the testicular immunoregulation is an important issue in reproductive immunology. In this proposal, we will use RNA and DNA viruses infected mouse model to investigate the correlation of RNA and DNA sensor-initiated innate antiviral response and orchitis, as well as their deleterious impacts on spermatogenesis. Two specific aims will be focused in this proposal: (1) to clarify the relationship between testicular innate immune response and inflammation through ligands activation or viral infection; (2) to study the molecular mechanism of RNA/DNA sensors mediated innate immune response by using RNAi technology and knockout mouse model. Outcomes of this study will provide novel insights into the mechanisms underlying the testicular innate immune responses and their effects on male fertility, which can aid in establishing preventive and therapeutic targets for virus-related male infertility. The project is expected to train 2-3 graduate students, and publish 2 papers on the professional SCI journals.