SARS-CoV2 infection in whole lung primarily targets macrophages that display subset-specific responses.
10X genomics
Azimuth software
Ex vivo lung perfusion
Viral nebulization
Journal
Cellular and molecular life sciences : CMLS
ISSN: 1420-9071
Titre abrégé: Cell Mol Life Sci
Pays: Switzerland
ID NLM: 9705402
Informations de publication
Date de publication:
15 Aug 2024
15 Aug 2024
Historique:
received:
09
11
2023
accepted:
05
06
2024
revised:
22
05
2024
medline:
16
8
2024
pubmed:
16
8
2024
entrez:
15
8
2024
Statut:
epublish
Résumé
Deciphering the initial steps of SARS-CoV-2 infection, that influence COVID-19 outcomes, is challenging because animal models do not always reproduce human biological processes and in vitro systems do not recapitulate the histoarchitecture and cellular composition of respiratory tissues. To address this, we developed an innovative ex vivo model of whole human lung infection with SARS-CoV-2, leveraging a lung transplantation technique. Through single-cell RNA-seq, we identified that alveolar and monocyte-derived macrophages (AMs and MoMacs) were initial targets of the virus. Exposure of isolated lung AMs, MoMacs, classical monocytes and non-classical monocytes (ncMos) to SARS-CoV-2 variants revealed that while all subsets responded, MoMacs produced higher levels of inflammatory cytokines than AMs, and ncMos contributed the least. A Wuhan lineage appeared to be more potent than a D614G virus, in a dose-dependent manner. Amidst the ambiguity in the literature regarding the initial SARS-CoV-2 cell target, our study reveals that AMs and MoMacs are dominant primary entry points for the virus, and suggests that their responses may conduct subsequent injury, depending on their abundance, the viral strain and dose. Interfering on virus interaction with lung macrophages should be considered in prophylactic strategies.
Identifiants
pubmed: 39147987
doi: 10.1007/s00018-024-05322-z
pii: 10.1007/s00018-024-05322-z
doi:
Substances chimiques
Cytokines
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
351Subventions
Organisme : Fondation pour la Recherche Médicale
ID : selection by the Flash ANR COVID-19 call
Informations de copyright
© 2024. The Author(s).
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