Portal de Periódicos da CAPES

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

2022; Nature Portfolio; Volume: 606; Issue: 7914 Linguagem: Inglês

10.1038/s41586-022-04702-4

1476-4687

Caroline Junqueira, Ângela C. Crespo, Shahin Ranjbar, Luna B. de Lacerda, Mercedes Lewandrowski, Jacob Ingber, Blair A. Parry, Sagi Ravid, Sarah A. Clark, Marie Rose Schrimpf, Felicia Ho, Caroline Beakes, Justin Margolin, Nicole Russell, Kyle R. Kays, Julie Boucau, Upasana Das Adhikari, Setu M. Vora, Valerie Leger, Lee Gehrke, Lauren A. Henderson, Erin Janssen, Douglas S. Kwon, Chris Sander, Jonathan Abraham, Marcia B. Goldberg, Hao Wu, Gautam Mehta, Steven Bell, Anne E. Goldfeld, Michael R. Filbin, Judy Lieberman,

SARS-CoV-2 and COVID-19 Research

SARS-CoV-2 can cause acute respiratory distress and death in some patients1. Although severe COVID-19 is linked to substantial inflammation, how SARS-CoV-2 triggers inflammation is not clear2. 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 mediators3. 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. 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.