1. FcγR-mediated SARS-CoV-2 infection of monocytes activates inflammation
- Author
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Caroline Junqueira, Ângela Crespo, Shahin Ranjbar, Luna B. de Lacerda, Mercedes Lewandrowski, Jacob Ingber, Blair Parry, Sagi Ravid, Sarah Clark, Marie Rose Schrimpf, Felicia Ho, Caroline Beakes, Justin Margolin, Nicole Russell, Kyle Kays, Julie Boucau, Upasana Das Adhikari, Setu M. Vora, Valerie Leger, Lee Gehrke, Lauren A. Henderson, Erin Janssen, Douglas Kwon, Chris Sander, Jonathan Abraham, Marcia B. Goldberg, Hao Wu, Gautam Mehta, Steven Bell, Anne E. Goldfeld, Michael R. Filbin, and Judy Lieberman
- Subjects
Inflammation ,Pore Forming Cytotoxic Proteins ,Multidisciplinary ,Inflammasomes ,SARS-CoV-2 ,Caspase 1 ,Receptors, IgG ,COVID-19 ,Phosphate-Binding Proteins ,Monocytes ,Article ,DNA-Binding Proteins ,NLR Family, Pyrin Domain-Containing 3 Protein ,Humans ,RNA, Viral ,Cytokine Release Syndrome - Abstract
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.
- Published
- 2022