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

Le résumé fourni par la source

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)

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.