Innate immune signaling in trophoblast and decidua organoids defines differential antiviral defenses at the maternal-fetal interface.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Yang, L; Semmes, EC; Ovies, C; Megli, C; Permar, S; Gilner, JB; Coyne, CB

Published Date

  • August 17, 2022

Published In

Volume / Issue

  • 11 /

PubMed ID

  • 35975985

Pubmed Central ID

  • PMC9470165

Electronic International Standard Serial Number (EISSN)

  • 2050-084X

Digital Object Identifier (DOI)

  • 10.7554/eLife.79794

Language

  • eng

Conference Location

  • England