title: Toll-like receptor 3 and RIG-I-like receptor activation induces innate antiviral responses in mouse ovarian granulosa cells.
abstract: Viral infections of the ovary can cause pathological conditions. However, innate antiviral responses in the ovary are poorly understood. In this study, we demonstrate that Toll-like receptor 3 (TLR3), retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated gene 5 (MDA5) are constitutively expressed in the mouse ovary and predominantly located in granulosa cells. Polyinosinic-polycytidylic acid [poly(I:C)], a common agonist of TLR3, MDA5 and RIG-I, induced innate antiviral responses in ovarian granulosa cells. Poly(I:C) up-regulated pro-inflammatory cytokines, including TNF-α and IL-6, and type I interferons (IFN-α/β). Moreover, poly(I:C) induced the expression of antiviral proteins, including 2'-5'-oligoadenylate synthetase, Mx GTPase 1 and IFN-stimulating gene 15, in granulosa cells. In contrast, P450 aromatase expression was inhibited by poly(I:C). The poly(I:C)-induced antiviral responses in TLR3 knockout (TLR3(-/-)) ovarian granulosa cells were reduced, and completely abolished by blocking of MDA5/RIG-I signaling. Further, the poly(I:C)-induced cytokine expression in TLR3(-/-) cells was reduced by knockdown of MDA5 or RIG-I. Data suggest that TLR3, MDA5 and RIG-I cooperate in mediating innate antiviral responses in granulosa cells, which may contribute to the defense of the ovary against viral infections.
authors.affiliation: Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, PR China.
authors.forename: Keqin
authors.initials: K
authors.lastname: Yan
authors.forename: Weiwei
authors.initials: W
authors.lastname: Zhu
authors.forename: Lili
authors.initials: L
authors.lastname: Yu
authors.forename: Nan
authors.initials: N
authors.lastname: Li
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhang
authors.forename: Peipei
authors.initials: P
authors.lastname: Liu
authors.forename: Qiaoyuan
authors.initials: Q
authors.lastname: Chen
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Chen
authors.forename: Daishu
authors.initials: D
authors.lastname: Han
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001141:Aromatase / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000276:immunology; D006107:Granulosa Cells / Q000276:immunology* / Q000378:metabolism; D007113:Immunity, Innate; D000072640:Interferon-Induced Helicase, IFIH1; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D064547:Myxovirus Resistance Proteins; D010053:Ovary / Q000166:cytology; D011070:Poly I-C / Q000494:pharmacology; D015398:Signal Transduction; D051196:Toll-Like Receptor 3 / Q000819:agonists / Q000378:metabolism*; D014452:Ubiquitins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D014777:Virus Diseases / Q000276:immunology
chemical_list: D016207:Cytokines; C489550:G1p2 protein, mouse; C579070:Mx1 protein, mouse; D064547:Myxovirus Resistance Proteins; C519703:TLR3 protein, mouse; D051196:Toll-Like Receptor 3; D014452:Ubiquitins; D001141:Aromatase; D015088:2',5'-Oligoadenylate Synthetase; C503356:Ddx58 protein, mouse; D019204:GTP-Binding Proteins; C510592:Ifih1 protein, mouse; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D011070:Poly I-C