SARS-CoV-2 induces inflammasome-dependent pyroptosis and downmodulation of HLA-DR in human monocytes, which can be prevented by atazanavir
Abstract Infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with leukopenia and uncontrolled inflammatory response in critically ill patients. A better comprehension of SARS-CoV-2-induced monocytes death is essential for the identification of therapies capable to control the hyper-inflammation and reduce viral replication in patients with COVID-19. Here, we show that SARS-CoV-2 induces inflammasome activation and cell death by pyroptosis in human monocytes, experimentally infected and in patients under intensive care. Pyroptosis was dependent on caspase-1 engagement, prior to IL-1ß production and inflammatory cell death. Monocytes exposed to SARS-CoV-2 downregulate HLA-DR, suggesting a potential limitation to orchestrate the immune response. Our results originally describe the mechanism by which monocytes, a central cellular component recruited from peripheral blood to respiratory tract, succumb in patients with severe 2019 coronavirus disease (COVID-19), and emphasize the need for identifying anti-inflammatory and antiviral strategies to prevent SARS-CoV-2-induced pyroptosis..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
bioRxiv.org - (2024) vom: 23. Apr. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ferreira, André C. [VerfasserIn] |
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| doi: |
10.1101/2020.08.25.20182055 |
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| PPN (Katalog-ID): |
XBI018652786 |
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| 520 | |a Abstract Infection by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with leukopenia and uncontrolled inflammatory response in critically ill patients. A better comprehension of SARS-CoV-2-induced monocytes death is essential for the identification of therapies capable to control the hyper-inflammation and reduce viral replication in patients with COVID-19. Here, we show that SARS-CoV-2 induces inflammasome activation and cell death by pyroptosis in human monocytes, experimentally infected and in patients under intensive care. Pyroptosis was dependent on caspase-1 engagement, prior to IL-1ß production and inflammatory cell death. Monocytes exposed to SARS-CoV-2 downregulate HLA-DR, suggesting a potential limitation to orchestrate the immune response. Our results originally describe the mechanism by which monocytes, a central cellular component recruited from peripheral blood to respiratory tract, succumb in patients with severe 2019 coronavirus disease (COVID-19), and emphasize the need for identifying anti-inflammatory and antiviral strategies to prevent SARS-CoV-2-induced pyroptosis. | ||
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| 700 | 1 | |a Mattos, Mayara |e verfasserin |4 aut | |
| 700 | 1 | |a de Freitas, Caroline S. |e verfasserin |4 aut | |
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| 700 | 1 | |a Teixeira, Lívia |e verfasserin |4 aut | |
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| 700 | 1 | |a Souza, Thiago Moreno L. |e verfasserin |4 aut | |
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