Interleukin 27 (IL-27) is an antiviral cytokine at the maternal-fetal interface 4478

Abstract Description During the critical developmental period of pregnancy, there are substantial consequences to infection. The placenta serves as a robust defense against congenital infection through its constitutive expression of antimicrobial cytokines. IL-27 is a highly expressed cytokine in the placenta, however its functional role at this barrier is unknown. In other contexts, IL-27 is immunoregulatory and is directly antiviral in human keratinocytes. Thus, our objective was to determine how IL-27 contributes to placental immune responses during congenital viral infection. We first utilized a human trophoblast organoid (TO) model to study IL-27 signaling in placental cells. We show that TOs recapitulate placental IL-27 expression in vitro, and that TOs exhibit higher Zika virus (ZIKV) burdens in the absence of IL-27 signaling. To further study placental IL-27 signaling during congenital viral infection, we next utilized an immunocompetent mouse model of congenital ZIKV. We obtained IL-27-deficient dams by routinely treating pregnant mice with IL-27-neutralizing antibody, or by genetic deletion of the IL-27 receptor. We found that infected, IL-27-deficient dams exhibited more pathologic fetal outcomes than control dams, despite similar fetal viral burdens. Interestingly, IL-27-deficient dams had significantly higher placental ZIKV burdens relative to control dams. In summary, these data identify a protective antiviral role for IL-27 in the placenta during congenital viral infection. Funding Sources Supported by NIH/NIAID 1R01AI180138-01, University of Pennsylvania Training Grant T32 GM-07229. Additional funding provided by the Linda Pechenik Montague Investigator Award and the Pew Charitable Trusts Biomedical Scholars Program. Topic Categories Mucosal and Regional Immunology (MUC)