Evaluating IL-27 production at the maternal-fetal interface and its role in innate antiviral immune defense during pregnancy

Abstract During pregnancy, it is critical to protect the womb and developing fetus from encountered pathogens. A way to enact protection is through localized immune cells. Immune cells communicate via specialized effector molecules called cytokines. Interleukin-27 (IL-27) is a cytokine that can initiate a pro-inflammatory or anti-inflammatory response, dependent on other microenvironmental queues. Interestingly, IL-27 and its receptor (IL27RA) are known to be expressed in the placenta throughout pregnancy. This research aims to mechanistically describe the functional role of IL-27 at the maternal-fetal interface. To accomplish this aim, we will use human trophoblast organoids to determine the kinetics of IL-27 by trophoblast cells. Additionally, we will use a murine model of pregnancy to assess IL-27 production and localization at the maternal-fetal interface in individual concepti. Localized production will be visualized using immunohistochemistry of implantation site cross-sections from an IL-27 reporter (p28-GFP) mouse. Our second aim is to determine the impact of IL-27 signaling on viral replication in our model systems using Zika virus as a model pathogen. We will determine the contribution of IL-27 to antiviral activities by assessing viral burden through transcriptional and immunofluorescence readouts. We hypothesize that IL-27, through autocrine signaling, induces constitutive antiviral programming that directly restricts viral replication in trophoblasts due to its ability to induce STAT1 signaling. Overall, this project will elucidate the presence and functionality of IL-27 at the maternal-fetal interface within murine and human models. Supported by grants from Pew Charitable Trusts Biomedical Scholars Program and Burroughs Wellcome fund