Interleukin 27 (IL-27): an immunoregulatory and antiviral cytokine at the maternal-fetal interface during congenital infection

Abstract

Abstract Cytokines maintain homeostasis throughout pregnancy and have diverse responses to pathogens at the maternal-fetal interface. Interleukin 27 (IL-27) is a cytokine that is highly expressed in the placenta, however its functional role during pregnancy is unknown. In other contexts, IL-27 is a potent regulator of inflammation and has been shown to mediate antiviral immunity in the skin. Therefore, our objective was to determine how IL-27 contributes to immune responses at the maternal-fetal interface during congenital viral infection. To begin, we utilized an immunocompetent mouse model for Zika virus (ZIKV) infection to assess pregnancy and infection outcomes in the presence and absence of IL-27 signaling. At gestational day 13.5, we observed that the fetuses of IL-27-competent and -deficient dams had similar ZIKV burdens. However, we observed a significantly higher incidence of fetal pathology (resorption) in IL-27-deficient dams. To identify potential effectors of pathology, I evaluated IL-27 receptor (IL27RA) expression in placental tissues using flow cytometry and immunofluorescence and detected IL27RA+ immune cells throughout the maternal-fetal interface. Together these findings suggest that fetal pathology is independent of ZIKV viral burden in IL-27-deficient mice, and that IL-27 signaling may dampen pathologic immune cell responses during pregnancy. Interestingly, the placental tissues of infected, IL-27-deficient dams had significantly higher ZIKV burdens relative to IL-27-competent dams, indicating a potential antiviral role for IL-27 in the placenta. In conclusion, these data support novel antiviral and immunoregulatory roles for IL-27 at the maternal-fetal interface during congenital viral infection. This work was supported by the University of Pennsylvania Cell and Molecular Biology Training Grant T32 GM-07229. Additional funding provided by the Linda Pechenik Montague Investigator Award and the Pew Charitable Trusts Biomedical Scholars Program.