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This study found that mouse epididymal epithelial cells (EECs) constitutively express several viral sensors, including TLR3, retinoic acid\u2013inducible 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\u2013inducible 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\u2032,5\u2032-oligoadenylate synthetase, and myxovirus resistance 1. Poly(I:C), but not HSV60, also dramatically induced the expression of major proinflammatory cytokines, including TNF-\u03b1 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.<\/jats:p>","DOI":"10.4049\/jimmunol.1402706","type":"journal-article","created":{"date-parts":[[2015,4,4]],"date-time":"2015-04-04T01:06:05Z","timestamp":1428109565000},"page":"4825-4835","source":"Crossref","is-referenced-by-count":31,"title":["Pattern Recognition Receptor\u2013Initiated Innate Antiviral Responses in Mouse Epididymal Epithelial Cells"],"prefix":"10.1093","volume":"194","author":[{"given":"Weiwei","family":"Zhu","sequence":"first","affiliation":[{"name":"School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences , Beijing 100005 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shutao","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences , Beijing 100005 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghui","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences , Beijing 100005 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijing","family":"Cheng","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences , Beijing 100005 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences , Beijing 100005 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keqin","family":"Yan","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences , Beijing 100005 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiaoyuan","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences , Beijing 100005 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han","family":"Wu","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences , Beijing 100005 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daishu","family":"Han","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences , Beijing 100005 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2015,5,15]]},"reference":[{"key":"2025030706233227400_r1","first-page":"583","article-title":"Epididymitis and orchitis: an overview","volume":"79","author":"Trojian","year":"2009","journal-title":"Am. 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Steril."},{"key":"2025030706233227400_r4","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1111\/j.1439-0272.2007.00825.x","article-title":"Sexually transmitted infections: impact on male fertility","volume":"40","author":"Ochsendorf","year":"2008","journal-title":"Andrologia"},{"key":"2025030706233227400_r5","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1126\/science.1183021","article-title":"Regulation of adaptive immunity by the innate immune system","volume":"327","author":"Iwasaki","year":"2010","journal-title":"Science"},{"key":"2025030706233227400_r6","doi-asserted-by":"crossref","first-page":"16","DOI":"10.3109\/08830185.2010.529976","article-title":"Pathogen recognition by the innate immune system","volume":"30","author":"Kumar","year":"2011","journal-title":"Int. Rev. 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