Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States
Eleanor C Semmes
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States; Duke Human Vaccine Institute, Duke University, Durham, United States
Cristian Ovies
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States
Christina Megli
Division of Maternal-Fetal Medicine, Division of Reproductive Infectious Disease, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh Medical Center (UPMC), Pittsburgh, United States; Magee Womens Research Institute, Pittsburgh, United States
Sallie Permar
Department of Pediatrics, Weill Cornell Medical Center, Duke University Medical Center, Durham, United States
Jennifer B Gilner
Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, United States
Department of Molecular Genetics and Microbiology, Duke University School of Medicine, Durham, United States; Duke Human Vaccine Institute, Duke University, Durham, United States
Infections at the maternal-fetal interface can directly harm the fetus and induce complications that adversely impact pregnancy outcomes. Innate immune signaling by both fetal-derived placental trophoblasts and the maternal decidua must provide antimicrobial defenses at this critical interface without compromising its integrity. Here, we developed matched trophoblast (TO) and decidua organoids (DO) from human placentas to define the relative contributions of these cells to antiviral defenses at the maternal-fetal interface. We demonstrate that TO and DO basally secrete distinct immunomodulatory factors, including the constitutive release of the antiviral type III interferon IFN-λ2 from TOs, and differentially respond to viral infections through the induction of organoid-specific factors. Finally, we define the differential susceptibility and innate immune signaling of TO and DO to human cytomegalovirus (HCMV) and develop a co-culture model of TO and DO which showed that trophoblast-derived factors protect decidual cells from HCMV infection. Our findings establish matched TO and DO as ex vivo models to study vertically transmitted infections and highlight differences in innate immune signaling by fetal-derived trophoblasts and the maternal decidua.
