Plate IV.262 · Publications
SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis
Article in Cell, December 2021.
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 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.
Cite
@article{wendisch2021sars,
title = {{SARS-CoV-2 infection triggers profibrotic macrophage responses and lung fibrosis}},
author = {Wendisch, Daniel and Dietrich, Oliver and Mari, Tommaso and von Stillfried, Saskia and Ibarra, Ignacio L. and Mittermaier, Mirja and Mache, Christin and Chua, Robert Lorenz and Knoll, Rainer and Timm, Sara and Brumhard, Sophia and Krammer, Tobias and Zauber, Henrik and Hiller, Anna Luisa and Pascual-Reguant, Anna and Mothes, Ronja and Bülow, Roman David and Schulze, Jessica and Leipold, Alexander M. and Djudjaj, Sonja and Erhard, Florian and Geffers, Robert and Pott, Fabian and Kazmierski, Julia and Radke, Josefine and Pergantis, Panagiotis and Baßler, Kevin and Conrad, Claudia and Aschenbrenner, Anna C. and Sawitzki, Birgit and Landthaler, Markus and Wyler, Emanuel and Horst, David and Hippenstiel, Stefan and Hocke, Andreas and Heppner, Frank L. and Uhrig, Alexander and Garcia, Carmen and Machleidt, Felix and Herold, Susanne and Elezkurtaj, Sefer and Thibeault, Charlotte and Witzenrath, Martin and Cochain, Clément and Suttorp, Norbert and Drosten, Christian and Goffinet, Christine and Kurth, Florian and Schultze, Joachim L. and Radbruch, Helena and Ochs, Matthias and Eils, Roland and Müller-Redetzky, Holger and Hauser, Anja E. and Luecken, Malte D. and Theis, Fabian J. and Conrad, Christian and Wolff, Thorsten and Boor, Peter and Selbach, Matthias and Saliba, Antoine-Emmanuel and Sander, Leif Erik},
journal = {Cell},
publisher = {Elsevier BV},
year = {2021},
month = dec,
doi = {10.1016/j.cell.2021.11.033},
url = {https://doi.org/10.1016/j.cell.2021.11.033},
pmid = {34914922},
pmcid = {PMC8626230}
}