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

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE

Publication: Basingstoke : Nature Publishing Group
Original Publication: London, Macmillan Journals ltd.

COVID-19*/virology ; Inflammation*/metabolism ; Inflammation*/virology ; Monocytes*/metabolism ; Monocytes*/virology ; Receptors, IgG*/metabolism ; SARS-CoV-2*; Caspase 1/metabolism ; DNA-Binding Proteins ; Humans ; Inflammasomes/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein ; Phosphate-Binding Proteins ; Pore Forming Cytotoxic Proteins

SARS-CoV-2 can cause acute respiratory distress and death in some patients ¹ . Although severe COVID-19 is linked to substantial inflammation, how SARS-CoV-2 triggers inflammation is not clear ² . Monocytes and macrophages are sentinel cells that sense invasive infection to form inflammasomes that activate caspase-1 and gasdermin D, leading to inflammatory death (pyroptosis) and the release of potent inflammatory mediators ³ . Here we show that about 6% of blood monocytes of patients with COVID-19 are infected with SARS-CoV-2. Monocyte infection depends on the uptake of antibody-opsonized virus by Fcγ receptors. The plasma of vaccine recipients 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 the supernatants of cultures of infected monocytes. Instead, infected cells undergo pyroptosis mediated by activation of NLRP3 and AIM2 inflammasomes, caspase-1 and gasdermin D. Moreover, tissue-resident macrophages, but not infected epithelial and endothelial cells, from lung autopsies from patients with COVID-19 have activated inflammasomes. Taken together, these findings suggest that antibody-mediated SARS-CoV-2 uptake by monocytes and macrophages triggers inflammatory cell death that aborts the production of infectious virus but causes systemic inflammation that contributes to COVID-19 pathogenesis.
(© 2022. The Author(s), under exclusive licence to Springer Nature Limited.)

Update of: Res Sq. 2021 Aug 11;:. (PMID: 34401873)
Comment in: Trends Immunol. 2022 Jun;43(6):417-419. (PMID: 35537983)
Comment in: Signal Transduct Target Ther. 2022 Jul 23;7(1):250. (PMID: 35871170)

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United Kingdom BHF_ British Heart Foundation; R01 AI124491 United States AI NIAID NIH HHS; T32 AI007245 United States AI NIAID NIH HHS; U19 AI131135 United States AI NIAID NIH HHS; P30 CA006516 United States CA NCI NIH HHS; P30 AI060354 United States AI NIAID NIH HHS

0 (AIM2 protein, human)
0 (DNA-Binding Proteins)
0 (GSDMD protein, human)
0 (Inflammasomes)
0 (NLR Family, Pyrin Domain-Containing 3 Protein)
0 (NLRP3 protein, human)
0 (Phosphate-Binding Proteins)
0 (Pore Forming Cytotoxic Proteins)
0 (Receptors, IgG)
EC 3.4.22.36 (Caspase 1)

Date Created: 20220406 Date Completed: 20220617 Latest Revision: 20240330

20240330

PMC10071495

10.1038/s41586-022-04702-4

35385861