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
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Online Access:https://doi.org/10.1038/s41598-025-08329-z
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author 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
author_facet 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
author_sort Chaillot Laura
collection DOAJ
description 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.
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institution Kabale University
issn 2045-2322
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publishDate 2025-07-01
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record_format Article
series Scientific Reports
spelling doaj-art-c5f212e743c449de9c4bbe961d27f46f2025-08-20T03:45:32ZengNature PortfolioScientific Reports2045-23222025-07-0115111510.1038/s41598-025-08329-zCXCL10-dependent epithelial-vascular cross-talk for endothelial activation following SARS-CoV-2 infectionChaillot Laura0Blondot Marie-Lise1Recordon-Pinson Patricia2Pellegrin Isabelle3Boizard-Moracchini Andrea4Sliusar Myroslava5Leboucq Teo6Pujol Nadege7Andreola Marie-Line8Bonnet Fabrice9Recher Gaelle10Andrique Laetitia11Nassoy Pierre12Mathivet Thomas13Bikfalvi Andreas14BRIC INSERM U1312, Université de BordeauxMFP Laboratory, UMR5234, CNRS Université de BordeauxMFP Laboratory, UMR5234, CNRS Université de BordeauxLaboratoire d’Immunologie-Immunogenetique, Centre de Ressources Biologiques Bordeaux Biothèques Santé (CRB-BBS), CHU de BordeauxLaboratoire d’Immunologie-Immunogenetique, Centre de Ressources Biologiques Bordeaux Biothèques Santé (CRB-BBS), CHU de BordeauxBRIC INSERM U1312, Université de BordeauxBRIC INSERM U1312, Université de BordeauxBRIC INSERM U1312, Université de BordeauxMFP Laboratory, UMR5234, CNRS Université de BordeauxService de Médecine Interne et Maladies Infectieuses, CHU de Bordeaux, Hôpital Saint-André, Université de Bordeaux, Bordeaux Population Health, INSERM U1219LP2N, Laboratoire Photonique Numérique et Nanosciences, Univ. BordeauxVoxCell 3D Facility UAR TBMcore CNRS, 3427-INSERMUS05, Université de BordeauxLP2N, Laboratoire Photonique Numérique et Nanosciences, Univ. BordeauxBRIC INSERM U1312, Université de BordeauxBRIC INSERM U1312, Université de BordeauxAbstract 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.https://doi.org/10.1038/s41598-025-08329-zEndotheliumSARS-CoV-2ChemokinesCXCL10
spellingShingle 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
CXCL10-dependent epithelial-vascular cross-talk for endothelial activation following SARS-CoV-2 infection
Scientific Reports
Endothelium
SARS-CoV-2
Chemokines
CXCL10
title CXCL10-dependent epithelial-vascular cross-talk for endothelial activation following SARS-CoV-2 infection
title_full CXCL10-dependent epithelial-vascular cross-talk for endothelial activation following SARS-CoV-2 infection
title_fullStr CXCL10-dependent epithelial-vascular cross-talk for endothelial activation following SARS-CoV-2 infection
title_full_unstemmed CXCL10-dependent epithelial-vascular cross-talk for endothelial activation following SARS-CoV-2 infection
title_short CXCL10-dependent epithelial-vascular cross-talk for endothelial activation following SARS-CoV-2 infection
title_sort cxcl10 dependent epithelial vascular cross talk for endothelial activation following sars cov 2 infection
topic Endothelium
SARS-CoV-2
Chemokines
CXCL10
url https://doi.org/10.1038/s41598-025-08329-z
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