Zhu Weiwei, Zhao Shutao, Liu Zhenghui, Cheng Lijing, Wang Qing, Yan Keqin, Chen Qiaoyuan, Wu Han, Han Daishu
School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China.
School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing 100005, China
J Immunol. 2015 May 15;194(10):4825-35. doi: 10.4049/jimmunol.1402706. Epub 2015 Apr 3.
Viral infections of the epididymis may impair male fertility and spread sexually transmitted pathogens. The innate antiviral immune responses in the epididymis have yet to be intensively investigated. This study found that mouse epididymal epithelial cells (EECs) constitutively express several viral sensors, including TLR3, retinoic acid-inducible gene I, and DNA-dependent activator of IFN regulatory factors. Other DNA sensors, including p204 and cGMP-AMP synthase, can be induced by transfection of synthetic HSV genomic DNA (HSV60). TLR3 and retinoic acid-inducible gene I in EECs can be activated by their common agonist, polyinosinic-polycytidylic acid [poly(I:C)]. The signaling pathway of DNA sensors can be initiated by HSV60. Both poly(I:C) and HSV60 induced the expression of type 1 IFNs and various antiviral proteins, including IFN-stimulated gene 15, 2',5'-oligoadenylate synthetase, and myxovirus resistance 1. Poly(I:C), but not HSV60, also dramatically induced the expression of major proinflammatory cytokines, including TNF-α and MCP-1, in EECs. In vivo assay confirmed that the local injection of poly(I:C) or HSV60 induced the innate antiviral responses in EECs. This study provided novel insights into the mechanisms underlying the innate antiviral responses in the mouse epididymis.
附睾的病毒感染可能损害男性生育能力并传播性传播病原体。附睾中的先天性抗病毒免疫反应尚未得到深入研究。本研究发现，小鼠附睾上皮细胞（EECs）组成性表达多种病毒传感器，包括Toll样受体3（TLR3）、视黄酸诱导基因I（RIG-I）和干扰素调节因子的DNA依赖性激活剂。其他DNA传感器，包括p204和环鸟苷酸-腺苷酸合成酶（cGAS），可通过转染合成的单纯疱疹病毒基因组DNA（HSV60）诱导产生。EECs中的TLR3和RIG-I可被其共同激动剂聚肌苷酸-聚胞苷酸[poly（I:C）]激活。DNA传感器的信号通路可由HSV60启动。poly（I:C）和HSV60均可诱导I型干扰素和多种抗病毒蛋白的表达，包括干扰素刺激基因15（ISG15）、2',5'-寡腺苷酸合成酶（OAS）和抗黏液病毒蛋白1（Mx1）。poly（I:C）而非HSV60还可显著诱导EECs中主要促炎细胞因子的表达，包括肿瘤坏死因子-α（TNF-α）和单核细胞趋化蛋白-1（MCP-1）。体内实验证实，局部注射poly（I:C）或HSV60可诱导EECs产生先天性抗病毒反应。本研究为小鼠附睾先天性抗病毒反应的潜在机制提供了新的见解。
