SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis

Autor: Anna Pascual-Reguant, Roman D. Bülow, Markus Landthaler, Fabian Pott, Mirja Mittermaier, Florian Erhard, Helena Radbruch, Carmen Garcia, Christian Conrad, Charlotte Thibeault, Alexander Uhrig, Robert Geffers, Peter Boor, Jessica Schulze, Anja E. Hauser, Sophia Brumhard, Antoine-Emmanuel Saliba, Stefan Hippenstiel, Anna Luisa Hiller, Emanuel Wyler, Fabian J. Theis, Tobias Krammer, Malte D Luecken, Sefer Elezkurtaj, Alexander M. Leipold, Sara Timm, Henrik Zauber, Leif E. Sander, Felix Machleidt, Frank L. Heppner, Rainer Knoll, Ronja Mothes, Panagiotis Pergantis, Roland Eils, Matthias Ochs, Oliver Dietrich, Saskia von Stillfried, Martin Witzenrath, Joachim L. Schultze, Florian Kurth, Christine Goffinet, Kevin Baßler, Anna C. Aschenbrenner, Robert Lorenz Chua, Tommaso Mari, Daniel Wendisch, Andreas C. Hocke, Christin Mache, Matthias Selbach, Josefine Radke, Susanne Herold, Ignacio L. Ibarra, Norbert Suttorp, Birgit Sawitzki, David Horst, Sonja Djudjaj, Claudia Conrad, Christian Drosten, Julia Kazmierski, Holger Müller-Redetzky, Clément Cochain, Thorsten Wolff
Přispěvatelé: HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany.
Jazyk: angličtina
Předmět:
pathology [Respiratory Distress Syndrome]
ARDS
metabolism [Antigens
CD]
metabolism [Receptors
Cell Surface]
Proteome
Transcription
Genetic
virology [COVID-19]
Cell Communication
pathology [Mesenchymal Stem Cells]
pathology [COVID-19]
Cohort Studies
Idiopathic pulmonary fibrosis
Pulmonary fibrosis
CD163 antigen
Macrophage
diagnostic imaging [COVID-19]
pathology [Idiopathic Pulmonary Fibrosis]
Respiratory Distress Syndrome
virology [Idiopathic Pulmonary Fibrosis]
virology [Respiratory Distress Syndrome]
Phenotype
macrophages
pathology [Fibroblasts]
genetics [Idiopathic Pulmonary Fibrosis]
monocytes
Antigens
Differentiation
Myelomonocytic
Receptors
Cell Surface
Biology
Lung injury
diagnostic imaging [Idiopathic Pulmonary Fibrosis]
Article
Ards
Covid-19
Fibrosis
Ipf
Lung
Macrophages
Monocytes
Proteomics
Pulmonary Fibrosis
Sars-cov-2
Single-cell Transcriptomics
General Biochemistry
Genetics and Molecular Biology
lung
virology [Macrophages]
proteomics
Immune system
Antigens
CD
medicine
Humans
ddc:610
physiology [SARS-CoV-2]
pulmonary fibrosis
SARS-CoV-2
fibrosis
COVID-19
Mesenchymal Stem Cells
metabolism [Proteome]
Fibroblasts
metabolism [Antigens
Differentiation
Myelomonocytic]
medicine.disease
Idiopathic Pulmonary Fibrosis
IPF
diagnostic imaging [Respiratory Distress Syndrome]
Gene Expression Regulation
Respiratory failure
Immunology
Tomography
X-Ray Computed
single-cell transcriptomics
pathology [Macrophages]
Zdroj: Cell
6261.e27
United States
Cell 184, 6243-6261.e27 (2021)
Cell 184(26), 6243-6261.e27 (2021). doi:10.1016/j.cell.2021.11.033
ISSN: 0092-8674
DOI: 10.1016/j.cell.2021.11.033
Popis: 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 analyzed 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.
SARS-CoV-2 infection, but not influenza A, triggers immunological and pathological changes in the lung that are hallmarks of pulmonary fibrosis. A subset of CD163+ macrophages are found to drive this fibroproliferative acute respiratory distress.
Databáze: OpenAIRE
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