title: Mumps virus-induced innate immune responses in mouse Sertoli and Leydig cells.
abstract: Mumps virus (MuV) infection frequently causes orchitis and impairs male fertility. However, the mechanisms underlying the innate immune responses to MuV infection in the testis have yet to be investigated. This study showed that MuV induced innate immune responses in mouse Sertoli and Leydig cells through TLR2 and retinoic acid-inducible gene I (RIG-I) signaling, which result in the production of proinflammatory cytokines and chemokines, including TNF-α, IL-6, MCP-1, CXCL10, and type 1 interferons (IFN-α and IFN-β). By contrast, MuV did not induce the cytokine production in male germ cells. In response to MuV infection, Sertoli cells produced higher levels of proinflammatory cytokines and chemokines but lower levels of type 1 IFNs than Leydig cells did. The MuV-induced cytokine production by Sertoli and Leydig cells was significantly reduced by the knockout of TLR2 or the knockdown of RIG-I signaling. The local injection of MuV into the testis triggered the testicular innate immune responses in vivo. Moreover, MuV infection suppressed testosterone synthesis by Leydig cells. This is the first study examining the innate immune responses to MuV infection in testicular cells. The results provide novel insights into the mechanisms underlying the MuV-induced innate immune responses in the testis.
authors.affiliation: School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Han
authors.initials: H
authors.lastname: Wu
authors.affiliation: School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Lili
authors.initials: L
authors.lastname: Shi
authors.affiliation: School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Lijing
authors.initials: L
authors.lastname: Cheng
authors.affiliation: School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhao
authors.affiliation: School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Qiaoyuan
authors.initials: Q
authors.lastname: Chen
authors.affiliation: School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, 650118, China.
authors.forename: Min
authors.initials: M
authors.lastname: Feng
authors.affiliation: Institute of Medical Biology, Chinese Academy of Medical Sciences, Kunming, 650118, China.
authors.forename: Qihan
authors.initials: Q
authors.lastname: Li
authors.affiliation: School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 100005, China.
authors.forename: Daishu
authors.initials: D
authors.lastname: Han
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D007985:Leydig Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009107:Mumps / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000821:virology*; D009109:Mumps virus / Q000276:immunology*; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface; D012708:Sertoli Cells / Q000276:immunology* / Q000378:metabolism / Q000821:virology; D013739:Testosterone / Q000096:biosynthesis; D051195:Toll-Like Receptor 2 / Q000235:genetics / Q000378:metabolism; D000097905:Roundabout Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D016207:Cytokines; D050838:Interferon Regulatory Factor-3; D008565:Membrane Proteins; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D011956:Receptors, Cell Surface; D013739:Testosterone; D051195:Toll-Like Receptor 2; C512612:MAVS protein, mouse; C118348:Robo3 protein, mouse; D000097905:Roundabout Proteins