Innate immune signaling in trophoblast and decidua organoids defines differential antiviral defenses at the maternal-fetal interface
- Duke University, United States
- University of Pittsburgh, United States
- Cornell University, United States
Abstract
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 and decidua organoids from human placentas to define the relative contributions of these cells to antiviral defenses at the maternal-fetal interface. We demonstrate that trophoblast and decidua organoids basally secrete distinct immunomodulatory factors, including the constitutive release of the antiviral type III interferon IFN-λ2 from trophoblast organoids, and differentially respond to viral infections through the induction of organoid-specific factors. Lastly, we define the differential susceptibility and innate immune signaling of trophoblast and decidua organoids to human cytomegalovirus (HCMV) and develop a co-culture model of trophoblast and decidua organoids which showed that trophoblast-derived factors protect decidual cells from HCMV infection. Our findings establish matched trophoblast and decidua organoids as ex vivo models to study vertically transmitted infections and highlight differences in innate immune signaling by fetal-derived trophoblasts and the maternal decidua.
Data availability
Sequence data have been deposited into Sequence Read Archives SUB11885513.
Article and author information
Author details
Funding
National Institute of Allergy and Infectious Diseases (NIHAI145828)
- Carolyn B Coyne
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Jan E Carette, Stanford University School of Medicine, United States
Publication history
- Preprint posted: March 30, 2021 (view preprint)
- Received: April 27, 2022
- Accepted: August 16, 2022
- Accepted Manuscript published: August 17, 2022 (version 1)
- Version of Record published: September 13, 2022 (version 2)
Copyright
© 2022, Yang et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Innate immune signaling in trophoblast and decidua organoids defines differential antiviral defenses at the maternal-fetal interface
eLife 11:e79794.
https://doi.org/10.7554/eLife.79794
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