Yan Keqin, Feng Dingqing, Liang Jing, Wang Qing, Deng Lin, Zhang Xiao, Ling Bin, Han Daishu
Department of Obstetrics and GynecologyChina-Japan Friendship Hospital, Beijing, China.
Institute of Basic Medical SciencesChinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
Reproduction. 2017 Jun;153(6):821-834. doi: 10.1530/REP-16-0674. Epub 2017 Mar 28.
Viral infections of the ovary may perturb ovarian functions. However, the mechanisms underlying innate immune responses in the ovary are poorly understood. The present study demonstrates that cytosolic viral DNA sensor signaling initiates the innate immune response in mouse ovarian granulosa cells and affects endocrine function. The cytosolic DNA sensors p204 and cGAS and their common signaling adaptor stimulator of interferon (IFN) genes (STING) were constitutively expressed in granulosa cells. Transfection with VACV70, a synthetic vaccinia virus (VACV) DNA analog, induced the expression of type I interferons (IFNA/B) and major inflammatory cytokines (TNFA and IL6) through IRF3 and NF-κB activation respectively. Moreover, several IFN-inducible antiviral proteins, including 2',5'-oligoadenylate synthetase, IFN-stimulating gene 15 and Mx GTPase 1, were also induced by VACV70 transfection. The innate immune responses in granulosa cells were significantly reduced by the transfection of specific small-interfering RNAs targeting , or Notably, the VACV70-triggered innate immune responses affected steroidogenesis and The data presented in this study describe the mechanism underlying ovarian immune responses to viral infection.
卵巢的病毒感染可能会扰乱卵巢功能。然而，卵巢中固有免疫反应的潜在机制仍知之甚少。本研究表明，胞质病毒DNA传感器信号传导启动了小鼠卵巢颗粒细胞中的固有免疫反应，并影响内分泌功能。胞质DNA传感器p204和cGAS及其共同的信号衔接子干扰素（IFN）基因刺激物（STING）在颗粒细胞中组成性表达。用合成痘苗病毒（VACV）DNA类似物VACV70转染，分别通过激活IRF3和NF-κB诱导I型干扰素（IFNA/B）和主要炎性细胞因子（TNFA和IL6）的表达。此外，VACV70转染还诱导了几种IFN诱导的抗病毒蛋白，包括2',5'-寡腺苷酸合成酶、IFN刺激基因15和Mx GTP酶1。靶向、或的特异性小干扰RNA转染显著降低了颗粒细胞中的固有免疫反应。值得注意的是，VACV70触发的固有免疫反应影响了类固醇生成和。本研究提供的数据描述了卵巢对病毒感染的免疫反应机制。
