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Cytosolic DNA sensor-initiated innate immune responses in mouse ovarian granulosa cells

Authors :
Bin Ling
Daishu Han
Lin Deng
Jing Liang
Xiao Zhang
Dingqing Feng
Keqin Yan
Qing Wang
Source :
Reproduction. 153:821-834
Publication Year :
2017
Publisher :
Bioscientifica, 2017.

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 targeting p204, cGas or Sting. Notably, the VACV70-triggered innate immune responses affected steroidogenesis in vivo and in vitro. The data presented in this study describe the mechanism underlying ovarian immune responses to viral infection.

Details

ISSN :
17417899 and 14701626
Volume :
153
Database :
OpenAIRE
Journal :
Reproduction
Accession number :
edsair.doi.dedup.....d46ae17b3dd44d31c1efabe28d5110fb
Full Text :
https://doi.org/10.1530/rep-16-0674