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: |
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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 |
Externí odkaz: |
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