| Autor: |
Loreen Thürmann, Felix Balzer, Jennifer Loske, Bernd Timmermann, Alexander Krannich, Robert Lorenz Chua, Florian Kurth, Christof von Kalle, Sven Laudi, Andreas C. Hocke, Christian Conrad, Johannes Liebig, Martin Witzenrath, Bianca P Hennig, Olivia Debnath, Fabian Pott, Roland Eils, Irina Lehmann, Soeren Lukassen, Naveed Ishaque, Felix Machleidt, Jürgen Eils, Sein Schmidt, Christian Drosten, Julia Kazmierski, Holger Müller-Redetzky, Christine Goffinet, Daniel Wendisch, Stefan Schneider, Sven Twardziok, Saskia Trump, Leif-Erik Sander |
| Rok vydání: |
2020 |
| Předmět: |
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| Popis: |
The clinical course of COVID-19 is highly variable, however, underlying host factors and determinants of severe disease are still unknown. Based on single-cell transcriptomes of nasopharyngeal and bronchial samples from clinically well-characterized patients presenting with moderate and critical severities, we reveal the different types and states of airway epithelial cells that are vulnerable for SARS-CoV-2 infection. In COVID-19 patients, we observed a two- to threefold increase of cells expressing the SARS-CoV-2 entry receptorACE2within the airway epithelial cell compartment.ACE2is upregulated in epithelial cells through Interferon signals by immune cells suggesting that the viral defense system may increase the number of potentially susceptible cells in the respiratory epithelium. Infected epithelial cells recruit and activate immune cells by chemokine signaling. Recruited T lymphocytes and inflammatory macrophages were hyperactivated and showed a strong interaction with epithelial cells. In critical patients, increased expression ofCCL2, CCL3, CCL5, CXCL9, CXCL10, IL8, IL1BandTNFin macrophages was identified as a likely cause of a hyperinflammatory lung pathology. Moreover, we observed exacerbated epithelial cell death, likely leading to lung injury and respiratory failure in fatal cases. Our study provides novel insights into the pathophysiology of COVID-19 and suggests an immunomodulatory therapy along the CCL2, CCL3/CCR1 axis as promising option to prevent and treat critical course of COVID-19. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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