| Autor: |
Shalini Pathak, Emily R. Watts, Manuel A. Sanchez-Garcia, Ananda S. Mirchandani, Azin Poon, Camila Takeno Cologna, Max Head Fourman, Moira K. B. Whyte, David M Griffith, David Hope, Sarah McNamara, Sarah K. Clark, Andrew J. M. Howden, Gio Rodriguez Blanco, Alejandro Brenes, Doreen A. Cantrell, Amy Lloyd, Kevin Dhaliwal, Isla Harper, Ailiang Zhang, Alex von Kriegsheim, Pranvera Sadiku, Nik Hirani, Leila Reyes, Tyler Morrison, Wesley Vermaelen, Shonna Johnston, Simone Arienti, David H. Dockrell, Sarah R. Walmsley, Patrícia Coelho, Jo Singleton, Bart Ghesquière, Robert Grecian |
| Rok vydání: |
2020 |
| Předmět: |
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| Popis: |
SummaryUnderstanding the mechanisms by which infection with SARS-CoV-2 leads to acute respiratory distress syndrome (ARDS) is of significant clinical interest given the mortality associated with severe and critical coronavirus induced disease 2019 (COVID-19). Neutrophils play a key role in the lung injury characteristic of non-COVID-19 ARDS, but a relative paucity of these cells is observed at post-mortem in lung tissue of patients who succumb to infection with SARS-CoV-2. With emerging evidence of a dysregulated innate immune response in COVID-19, we undertook a functional proteomic survey of circulating neutrophil populations, comparing patients with COVID-19 ARDS, non-COVID-19 ARDS, moderate COVID-19, and healthy controls. We observe that expansion of the circulating neutrophil compartment and the presence of activated low and normal density mature and immature neutrophil populations occurs in both COVID-19 and non-COVID-19 ARDS. In contrast, release of neutrophil granule proteins, neutrophil activation of the clotting cascade and formation of neutrophil platelet aggregates is significantly increased in COVID-19 ARDS. Importantly, activation of components of the neutrophil type I IFN responses is specific to infection with SARS-CoV-2 and linked to metabolic rewiring. Together this work highlights how differential activation of circulating neutrophil populations may contribute to the pathogenesis of ARDS, identifying processes that are specific to COVID-19 ARDS. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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