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FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation

Junqueira, Caroline; Crespo, Ângela; Ranjbar, Shahin; De Lacerda, Luna B; Lewandrowski, Mercedes; Ingber, Jacob; Parry, Blair; ... Lieberman, Judy; + view all (2022) FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation. Nature , 606 pp. 576-584. 10.1038/s41586-022-04702-4. Green open access

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Abstract

SARS-CoV-2 can cause acute respiratory distress and death in some patients1. Although severe COVID-19 disease is linked to exuberant inflammation, how SARS-CoV-2 triggers inflammation is not understood2. 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 mediators3. 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-dependent 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.

Type: Article
Title: FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1038/s41586-022-04702-4
Publisher version: https://doi.org/10.1038/s41586-022-04702-4
Language: English
Additional information: This version is the author accepted manuscript. For information on re-use, please refer to the publisher’s terms and conditions.
Keywords: Antimicrobial responses, Immune cell death, Monocytes and macrophages, SARS-CoV-2
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Inst for Liver and Digestive Hlth
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
URI: https://discovery.ucl.ac.uk/id/eprint/10149998
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