CXCL10-dependent epithelial-vascular cross-talk for endothelial activation following SARS-CoV-2 infection

CXCL10-dependent epithelial-vascular cross-talk for endothelial activation following SARS-CoV-2 infection

Abstract The blood vessel network is heavily impacted by SARS-CoV-2 infection. How SARS-CoV-2 contributes to vascular inflammation and whether epithelio-endothelial cross-talk is involved remain unclear. We investigated in detail the interaction between SARS-CoV-2 and the vasculature using 2D and 3D...

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Main Authors: Chaillot Laura, Blondot Marie-Lise, Recordon-Pinson Patricia, Pellegrin Isabelle, Boizard-Moracchini Andrea, Sliusar Myroslava, Leboucq Teo, Pujol Nadege, Andreola Marie-Line, Bonnet Fabrice, Recher Gaelle, Andrique Laetitia, Nassoy Pierre, Mathivet Thomas, Bikfalvi Andreas
Format: Article
Language:English
Published: Nature Portfolio 2025-07-01
Series:Scientific Reports
Subjects:
Endothelium
SARS-CoV-2
Chemokines
CXCL10
Online Access:https://doi.org/10.1038/s41598-025-08329-z
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Summary:Abstract The blood vessel network is heavily impacted by SARS-CoV-2 infection. How SARS-CoV-2 contributes to vascular inflammation and whether epithelio-endothelial cross-talk is involved remain unclear. We investigated in detail the interaction between SARS-CoV-2 and the vasculature using 2D and 3D vesseloid in vitro models. We first assessed whether SARS-CoV-2 is able to directly infect endothelial cells. In the absence of ACE2 in endothelial cells, no productive infection was detected. Low uptake of viral particles by ACE2-overexpressing endothelial cells was observed without efficient viral production. Thus, the indirect effect of SARS-CoV-2 infection may involve epithelio-endothelial cell cross-talk. After infection of the epithelial cells, a significant inflammatory response was detected in the endothelial cells. CXCL10 was the most highly expressed proinflammatory cytokine involved in this intercellular communication, and its function was subsequently explored. Finally, the clinical relevance of our findings was confirmed in two patient cohorts.
ISSN:2045-2322

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