SARS-CoV-2 infects blood monocytes via FcγR and activates inflammation
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Journal Title
Nature
ISSN
0028-0836
Publisher
Nature Research
Type
Article
This Version
AM
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Junqueira, C., Crespo, Â., Ranjbar, S., Bell, S., Filbin, M., & Lieberman, J. SARS-CoV-2 infects blood monocytes via FcγR and activates inflammation. Nature https://doi.org/10.17863/CAM.82919
Abstract
SARS-CoV-2 can cause acute respiratory distress and death in some patients. Although severe COVID-19 disease is linked to exuberant inflammation, how SARS-CoV-2 triggers inflammation is not understood. Monocytes and macrophages are sentinel cells that sense invasive infection to form inflammasomes that activate caspase-1 and gasdermin D (GSDMD), leading to inflammatory death (pyroptosis) and release of potent inflammatory mediators. Here we show that about 6% of blood monocytes in COVID-19 patients are infected with SARS-CoV-2. Monocyte infection depends on uptake of antibody-opsonized virus by Fcγ receptors. Vaccine recipient plasma does not promote antibody-enhanced monocyte infection. SARS-CoV-2 begins to replicate in monocytes, but infection is aborted, and infectious virus is not detected in infected monocyte culture supernatants. Instead, infected cells undergo inflammatory cell death (pyroptosis) mediated by activation of NLRP3 and AIM2 inflammasomes, caspase-1 and GSDMD. Moreover, tissue-resident macrophages, but not infected epithelial and endothelial cells, from COVID-19 lung autopsies have activated inflammasomes. These findings taken together suggest that antibody-mediated SARS-CoV-2 uptake by monocytes/macrophages triggers inflammatory cell death that aborts production of infectious virus but causes systemic inflammation that contributes to COVID-19 pathogenesis.
Embargo Lift Date
2025-03-29
Identifiers
This record's DOI: https://doi.org/10.17863/CAM.82919
This record's URL: https://www.repository.cam.ac.uk/handle/1810/335488
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