SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis.
Antigens, CD
/ metabolism
Antigens, Differentiation, Myelomonocytic
/ metabolism
COVID-19
/ diagnostic imaging
Cell Communication
Cohort Studies
Fibroblasts
/ pathology
Gene Expression Regulation
Humans
Idiopathic Pulmonary Fibrosis
/ diagnostic imaging
Macrophages
/ pathology
Mesenchymal Stem Cells
/ pathology
Phenotype
Proteome
/ metabolism
Receptors, Cell Surface
/ metabolism
Respiratory Distress Syndrome
/ diagnostic imaging
SARS-CoV-2
/ physiology
Tomography, X-Ray Computed
Transcription, Genetic
ARDS
COVID-19
IPF
SARS-CoV-2
fibrosis
lung
macrophages
monocytes
proteomics
pulmonary fibrosis
single-cell transcriptomics
Journal
Cell
ISSN: 1097-4172
Titre abrégé: Cell
Pays: United States
ID NLM: 0413066
Informations de publication
Date de publication:
22 12 2021
22 12 2021
Historique:
received:
30
11
2020
revised:
28
07
2021
accepted:
23
11
2021
pubmed:
17
12
2021
medline:
6
1
2022
entrez:
16
12
2021
Statut:
ppublish
Résumé
COVID-19-induced "acute respiratory distress syndrome" (ARDS) is associated with prolonged respiratory failure and high mortality, but the mechanistic basis of lung injury remains incompletely understood. Here, we analyze pulmonary immune responses and lung pathology in two cohorts of patients with COVID-19 ARDS using functional single-cell genomics, immunohistology, and electron microscopy. We describe an accumulation of CD163-expressing monocyte-derived macrophages that acquired a profibrotic transcriptional phenotype during COVID-19 ARDS. Gene set enrichment and computational data integration revealed a significant similarity between COVID-19-associated macrophages and profibrotic macrophage populations identified in idiopathic pulmonary fibrosis. COVID-19 ARDS was associated with clinical, radiographic, histopathological, and ultrastructural hallmarks of pulmonary fibrosis. Exposure of human monocytes to SARS-CoV-2, but not influenza A virus or viral RNA analogs, was sufficient to induce a similar profibrotic phenotype in vitro. In conclusion, we demonstrate that SARS-CoV-2 triggers profibrotic macrophage responses and pronounced fibroproliferative ARDS.
Identifiants
pubmed: 34914922
pii: S0092-8674(21)01383-0
doi: 10.1016/j.cell.2021.11.033
pmc: PMC8626230
pii:
doi:
Substances chimiques
Antigens, CD
0
Antigens, Differentiation, Myelomonocytic
0
CD163 antigen
0
Proteome
0
Receptors, Cell Surface
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
6243-6261.e27Informations de copyright
Copyright © 2021. Published by Elsevier Inc.
Déclaration de conflit d'intérêts
Declaration of interests The authors declare no competing interests.
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