Estrogen inhibits dendritic cell maturation to RNA viruses

Abstract

Dendritic cells (DCs) play a central role in initiating and polarizing the immune response. Therefore, DC maturation represents a key control point in the shift from innate to adaptive immunity. It is suspected that during pregnancy, hormones are critical factors that modulate changes reported to occur in maternal immunity. Here we examined the effect of 17-beta-estradiol (E2) on the maturational response triggered by virus in human DCs and its influence on their ability to activate naive T cells. We developed an in vitro system to measure the response of DCs to virus infection with Newcastle disease virus (NDV) after a 24-hour E2 treatment. Using this system, we demonstrated that E2 pretreatment down-regulated the antiviral response to RNA viruses in DCs by profoundly suppressing type I interferon (IFN) synthesis and other important inflammatory products. In addition, the DCs capacity to stimulate naive CD4 T cells was also reduced. These results suggest an important role for E2 in suppressing the antiviral response and provide a mechanism for the reduced immunity to virus infection observed during pregnancy.

Caspase-12 controls West Nile virus infection via the viral RNA receptor RIG-I

“…Notably, estrogen has also been shown to downregulate the antiviral response to RNA viruses in dendritic cells by suppressing the production of type I interferon 49 . It is plausible that estrogen affects the production of type I interferon in response to viral infection partly because of its effect on caspase-12 expression.…”

Endocrine Regulation of the Mucosal Immune System in the Female Reproductive Tract

“…Type I and type III IFN secretion and interferon stimulated genes (ISGs) expression by human uterine ECs is unaffected by E 2 concentration, which suggests that IFN-mediated protection at the epithelium is relatively constant across the menstrual cycle (Patel et al, 2012). However, other studies have shown an effect on IFN and ISG expression by E 2 , which indicates that the interaction of hormone and IFN response pathway is complex and may depend on cell type and location within the FRT (Escribese et al, 2008;Li et al, 2001). Previous studies have demonstrated a role for hormonal regulation of antimicrobial and cytokine production in vivo in the FRT.…”

Immune Cells Have Sex and So Should Journal Articles

“…E2 also regulates innate immune responses, including production of proinflammatory cytokines, by selectively up-and downregulating microRNA (miRNA) (44). Estradiol affects the differentiation and functioning of APC, including DC (45,46). E2 can have bipotential effects on inflammatory responses, with low doses enhancing proinflammatory cytokine production (e.g.…”