Article (Scientific journals)
Central role of lung macrophages in SARS-CoV-2 physiopathology: a cross-model single-cell RNA-seq perspective.
Olivier, Thibaut; Blomet, Joël; Desmecht, Daniel
2023In Frontiers in Immunology, 14, p. 1197588
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Keywords :
FcγR; M1 macrophages; SARS-CoV-2; antibody-dependent enhancement; cytokine storm; interferons; Interferons; Cytokines; Animals; Chlorocebus aethiops; Single-Cell Gene Expression Analysis; Interferons/metabolism; Alveolar Epithelial Cells/metabolism; Cytokines/metabolism; Macrophages/metabolism; COVID-19/metabolism; Alveolar Epithelial Cells; COVID-19; Macrophages; Immunology and Allergy; Immunology
Abstract :
[en] Cytokine storms are considered a driving factor in coronavirus disease 2019 (COVID-19) severity. However, the triggering and resolution of this cytokine production, as well as the link between this phenomenon and infected cells, are still poorly understood. In this study, a cross-species scRNA-seq analysis showed that cytokine-producing macrophages together with pneumocytes were found to be the main contributors of viral transcripts in both Syrian hamsters and African green monkeys. Whatever the cell type, viral read-bearing cells show an apoptotic phenotype. A comparison of SARS-CoV-2 entry receptor candidates showed that Fc receptors are better correlated with infected cells than ACE2, NRP1, or AXL. Although both species show similar interferon responses, differences in adaptive immunity were highlighted. Lastly, Fc receptor and cytokine upregulation in M1 macrophages was found to correlate with a comprehensive interferon response. Based on these results, we propose a model in which lung macrophages play a central role in COVID-19 severity through antibody-dependent enhancement.
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Olivier, Thibaut ;  Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Santé publique vétérinaire ; GAS Department, Prevor Research Laboratories, Valmondois, France
Blomet, Joël;  GAS Department, Prevor Research Laboratories, Valmondois, France
Desmecht, Daniel ;  Université de Liège - ULiège > Département de morphologie et pathologie (DMP) > Pathologie spéciale et autopsies
Language :
English
Title :
Central role of lung macrophages in SARS-CoV-2 physiopathology: a cross-model single-cell RNA-seq perspective.
Alternative titles :
[fr] Rôle central des macrophages pulmonaires dans la physiopathologie du SARS-CoV-2: une perspective inter-modèle basée sur le séquençage des ARN en cellules uniques
Publication date :
2023
Journal title :
Frontiers in Immunology
eISSN :
1664-3224
Publisher :
Frontiers Media S.A., Switzerland
Volume :
14
Pages :
1197588
Peer reviewed :
Peer Reviewed verified by ORBi
Tags :
CÉCI : Consortium des Équipements de Calcul Intensif
Funders :
Prevor SPRL [BE]
Funding text :
This work was supported by Prevor SPRL.
Available on ORBi :
since 29 September 2023

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