title: Mumps virus induces innate immune responses in mouse ovarian granulosa cells through the activation of Toll-like receptor 2 and retinoic acid-inducible gene I.
abstract: Mumps virus (MuV) infection may lead to oophoritis and perturb ovarian function. However, the mechanisms underlying the activation of innate immune responses to MuV infection in the ovary have not been investigated. This study showed that Toll-like receptor 2 (TLR2) and retinoic acid-inducible gene I (RIG-I) cooperatively initiate innate immune responses to MuV infection in mouse ovarian granulosa cells. Ovarian granulosa cells infected with MuV significantly produced pro-inflammatory cytokines and chemokines, including interleukin-1β (IL-1β), tumor necrosis factor α (TNF-α), monocyte chemotactic protein 1 (MCP-1), and type 1 interferons (IFN-α and IFN-β). Knockdown of RIG-I significantly decreased MuV-induced cytokine expression. TLR2 deficiency reduced the expression of IL-1β, TNF-α, and MCP-1 but did not affect the expression of IFN-α and IFN-β in granulosa cells after infection with MuV. Intraperitoneal injection of MuV induced the ovarian innate immune responses in vivo, which suppressed estradiol synthesis and induced granulosa cell apoptosis. The results provide novel insights into the mechanisms underlying MuV-induced innate immune responses in the mouse ovary.
authors.affiliation: School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 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, 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, 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, China.
authors.forename: Keqin
authors.initials: K
authors.lastname: Yan
authors.affiliation: School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, 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, 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, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Wang
authors.affiliation: School of Basic Medicine, Peking Union Medical College, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Beijing, China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Chen
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, China. Electronic address: dshan@ibms.pumc.edu.cn.
authors.forename: Daishu
authors.initials: D
authors.lastname: Han
mesh_terms: D000818:Animals; D017209:Apoptosis; D016207:Cytokines / Q000378:metabolism; D000071457:DEAD Box Protein 58 / Q000378:metabolism*; D005260:Female; D006107:Granulosa Cells / Q000276:immunology* / Q000821:virology*; D006801:Humans; D007113:Immunity, Innate; D050838:Interferon Regulatory Factor-3 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009107:Mumps / Q000276:immunology / Q000821:virology; D009109:Mumps virus / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D050838:Interferon Regulatory Factor-3; C494233:Irf3 protein, mouse; D016328:NF-kappa B; D051195:Toll-Like Receptor 2; C503356:Ddx58 protein, mouse; D000071457:DEAD Box Protein 58
keywords: Innate immune response; Mumps virus; Ovarian granulosa cell; Pattern recognition receptor