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

Caroline Junqueira (), Ângela Crespo, Shahin Ranjbar, Luna B. 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 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 ()
Additional contact information
Caroline Junqueira: Boston Children’s Hospital
Ângela Crespo: Boston Children’s Hospital
Shahin Ranjbar: Boston Children’s Hospital
Luna B. Lacerda: Boston Children’s Hospital
Mercedes Lewandrowski: Boston Children’s Hospital
Jacob Ingber: Boston Children’s Hospital
Blair Parry: Massachusetts General Hospital
Sagi Ravid: Boston Children’s Hospital
Sarah Clark: Harvard Medical School
Marie Rose Schrimpf: Boston Children’s Hospital
Felicia Ho: Boston Children’s Hospital
Caroline Beakes: Massachusetts General Hospital
Justin Margolin: Massachusetts General Hospital
Nicole Russell: Massachusetts General Hospital
Kyle Kays: Massachusetts General Hospital
Julie Boucau: Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard Medical School
Upasana Adhikari: Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard Medical School
Setu M. Vora: Boston Children’s Hospital
Valerie Leger: Massachusetts Institute of Technology
Lee Gehrke: Harvard Medical School
Lauren A. Henderson: Harvard Medical School
Erin Janssen: Harvard Medical School
Douglas Kwon: Massachusetts General Hospital, Massachusetts Institute of Technology, Harvard Medical School
Chris Sander: Harvard Medical School
Jonathan Abraham: Harvard Medical School
Marcia B. Goldberg: Harvard Medical School
Hao Wu: Boston Children’s Hospital
Gautam Mehta: University College London
Steven Bell: University of Cambridge
Anne E. Goldfeld: Boston Children’s Hospital
Michael R. Filbin: Massachusetts General Hospital
Judy Lieberman: Boston Children’s Hospital

Nature, 2022, vol. 606, issue 7914, 576-584

Abstract: Abstract 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.

Date: 2022
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DOI: 10.1038/s41586-022-04702-4

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