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

IRF3 prevents colorectal tumorigenesis via inhibiting the nuclear translocation of β-catenin

“…S6c). In line with the previous report 35 , IRF3 deficiency significantly inhibited type I interferon and ISG expression, but had no effect on IL6 and TNFα expression ( Supplementary Fig. S6d, e).…”

Polyinosinic‐polycytidylic acid induces innate immune responses via Toll‐like receptor 3 in human ovarian granulosa cells

“…Increased TNF‐α, IL‐6 and IL‐1β interfere with estradiol and inhibin synthesis . Our previous study demonstrated that increased TNF‐α in mouse ovary suppresses estradiol synthesis and induces antral follicle granulosa cell apoptosis through TNFR1 . The present study showed that human ovarian granulosa cells produced significantly high levels of TNF‐α, IL‐6 and IL‐1β in response to poly (I:C) treatment, whereas cytochrome aromatase (P450arom) and inhibin were dramatically decreased after poly (I:C) treatment.…”

“…Ovarian tissues were used for immunohistochemistry studies according to previously described procedures . Briefly, the fixed ovarian tissues were embedded in paraffin and cut into 5‐μm‐thick sections.…”

“…The protein contents of the cell lysates were quantified by western blotting as described previously . Twenty micrograms of total proteins were separated on 10% SDS‐PAGE gels and electrotransferred onto polyvinyl difluoride membranes (Millipore, Bedford, MA, USA).…”

“…IFN‐α/β production then induces the expression of multiple antiviral proteins to protect against viral invasion, such as IFN‐stimulated gene 15, Mx GTPase 1, 2′‐5′‐oligoadenylate synthetase and double‐stranded‐activated protein kinase R . However, the PRR‐induced inflammatory milieu may damage tissue function …”