title: Cytosolic DNA sensor-initiated innate immune responses in mouse ovarian granulosa cells.
abstract: Viral infections of the ovary may perturb ovarian functions. However, the mechanisms underlying innate immune responses in the ovary are poorly understood. The present study demonstrates that cytosolic viral DNA sensor signaling initiates the innate immune response in mouse ovarian granulosa cells and affects endocrine function. The cytosolic DNA sensors p204 and cGAS and their common signaling adaptor stimulator of interferon (IFN) genes (STING) were constitutively expressed in granulosa cells. Transfection with VACV70, a synthetic vaccinia virus (VACV) DNA analog, induced the expression of type I interferons (IFNA/B) and major inflammatory cytokines (TNFA and IL6) through IRF3 and NF-κB activation respectively. Moreover, several IFN-inducible antiviral proteins, including 2',5'-oligoadenylate synthetase, IFN-stimulating gene 15 and Mx GTPase 1, were also induced by VACV70 transfection. The innate immune responses in granulosa cells were significantly reduced by the transfection of specific small-interfering RNAs targetingp204,cGasorStingNotably, the VACV70-triggered innate immune responses affected steroidogenesisin vivoandin vitroThe data presented in this study describe the mechanism underlying ovarian immune responses to viral infection.
authors.affiliation: Department of Obstetrics and GynecologyChina-Japan Friendship Hospital, Beijing, China.
authors.forename: Keqin
authors.initials: K
authors.lastname: Yan
authors.affiliation: Department of Obstetrics and GynecologyChina-Japan Friendship Hospital, Beijing, China.
authors.forename: Dingqing
authors.initials: D
authors.lastname: Feng
authors.affiliation: Department of Obstetrics and GynecologyChina-Japan Friendship Hospital, Beijing, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Liang
authors.affiliation: Institute of Basic Medical SciencesChinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Obstetrics and GynecologyChina-Japan Friendship Hospital, Beijing, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Deng
authors.affiliation: Department of Obstetrics and GynecologyChina-Japan Friendship Hospital, Beijing, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Obstetrics and GynecologyChina-Japan Friendship Hospital, Beijing, China lingbin.ling@vip.sina.com dshan@ibms.pumc.edu.cn.
authors.forename: Bin
authors.initials: B
authors.lastname: Ling
authors.affiliation: Institute of Basic Medical SciencesChinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, China lingbin.ling@vip.sina.com dshan@ibms.pumc.edu.cn.
authors.forename: Daishu
authors.initials: D
authors.lastname: Han
mesh_terms: D000818:Animals; D003600:Cytosol / Q000378:metabolism*; D004279:DNA, Viral / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D005260:Female; D006107:Granulosa Cells / Q000187:drug effects / Q000276:immunology*; D007113:Immunity, Innate / Q000187:drug effects / Q000276:immunology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D009713:Nucleotidyltransferases / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D015398:Signal Transduction; D000099197:STING Protein; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase
chemical_list: D004279:DNA, Viral; D008565:Membrane Proteins; D016328:NF-kappa B; D009687:Nuclear Proteins; D009713:Nucleotidyltransferases; D010750:Phosphoproteins; C489664:Ifi16 protein, mouse; C530855:Sting1 protein, mouse; D000099197:STING Protein; C578391:cGAS protein, mouse; D000099235:Cyclic Guanosine Monophosphate-Adenosine Monophosphate Synthase