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

Item Type:Article
Title:SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis
Creators Name:Wendisch, D. and Dietrich, O. and Mari, T. and von Stillfried, S. and Ibarra, I.L. and Mittermaier, M. and Mache, C. and Chua, R.L. and Knoll, R. and Timm, S. and Brumhard, S. and Krammer, T. and Zauber, H. and Hiller, A.L. and Pascual-Reguant, A. and Mothes, R. and Bülow, R.D. and Schulze, J. and Leipold, A.M. and Djudjaj, S. and Erhard, F. and Geffers, R. and Pott, F. and Kazmierski, J. and Radke, J. and Pergantis, P. and Baßler, K. and Conrad, C. and Aschenbrenner, A.C. and Sawitzki, B. and Landthaler, M. and Wyler, E. and Horst, D. and Hippenstiel, S. and Hocke, A. and Heppner, F.L. and Uhrig, A. and Garcia, C. and Machleidt, F. and Herold, S. and Elezkurtaj, S. and Thibeault, C. and Witzenrath, M. and Cochain, C. and Suttorp, N. and Drosten, C. and Goffinet, C. and Kurth, F. and Schultze, J.L. and Radbruch, H. and Ochs, M. and Eils, R. and Müller-Redetzky, H. and Hauser, A.E. and Luecken, M.D. and Theis, F.J. and Conrad, C. and Wolff, T. and Boor, P. and Selbach, M. and Saliba, A.E. and Sander, L.E.
Abstract: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.
Keywords:CD Antigens, COVID-19, Cell Communication, Cell Surface Receptors, Cohort Studies, Fibroblasts, Gene Expression Regulation, Genetic Transcription, Idiopathic Pulmonary Fibrosis, Macrophages, Mesenchymal Stem Cells, Myelomonocytic Differentiation Antigens, Phenotype, Proteome, Respiratory Distress Syndrome, SARS-CoV-2, X-Ray Computed Tomography
Source:Cell
ISSN:0092-8674
Publisher:Cell Press
Volume:184
Number:26
Page Range:6243-6261
Date:22 December 2021
Official Publication:https://doi.org/10.1016/j.cell.2021.11.033
PubMed:View item in PubMed

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