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Cytosolic DNA sensor-initiated innate immune responses in mouse ovarian granulosa cells
- 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.
- Subjects :
- 0301 basic medicine
Embryology
viruses
Biology
Mice
03 medical and health sciences
Cytosol
Endocrinology
Immune system
Immunity
Interferon
medicine
Animals
Granulosa Cells
Innate immune system
NF-kappa B
Membrane Proteins
Nuclear Proteins
Obstetrics and Gynecology
Cell Biology
Transfection
Phosphoproteins
Nucleotidyltransferases
Immunity, Innate
Cell biology
Mice, Inbred C57BL
030104 developmental biology
Reproductive Medicine
DNA, Viral
Immunology
Female
Tumor necrosis factor alpha
Signal transduction
IRF3
Signal Transduction
medicine.drug
Subjects
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