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https://www.arca.fiocruz.br/handle/icict/52090
FCγR-MEDIATED SARS-COV-2 INFECTION OF MONOCYTES ACTIVATES INFLAMMATION
Author
Junqueira, Caroline
Crespo, Ângela
Ranjbar, Shahin
Lacerda, Luna B. de
Lewandrowski, Mercedes
Ingber, Jacob
Parry, Blair
Ravid, Sagi
Clark, Sarah
Schrimpf, Marie Rose
Ho, Felicia
Beakes, Caroline
Margolin, Justin
Russell, Nicole
Kays, Kyle
Boucau, Julie
Adhikar, Upasana Das
Vora, Setu M.
Leger, Valerie
Gehrke, Lee
Henderson, Lauren
Janssen, Erin
Kwon, Douglas
Sander, Chris
Abraham, Jonathan
Goldberg, Marcia B.
Hao, Wu
Mehta, Gautam
Bell, Steven
Goldfeld, Anne E.
Filbin, Michael R.
Lieberman, Judy
Crespo, Ângela
Ranjbar, Shahin
Lacerda, Luna B. de
Lewandrowski, Mercedes
Ingber, Jacob
Parry, Blair
Ravid, Sagi
Clark, Sarah
Schrimpf, Marie Rose
Ho, Felicia
Beakes, Caroline
Margolin, Justin
Russell, Nicole
Kays, Kyle
Boucau, Julie
Adhikar, Upasana Das
Vora, Setu M.
Leger, Valerie
Gehrke, Lee
Henderson, Lauren
Janssen, Erin
Kwon, Douglas
Sander, Chris
Abraham, Jonathan
Goldberg, Marcia B.
Hao, Wu
Mehta, Gautam
Bell, Steven
Goldfeld, Anne E.
Filbin, Michael R.
Lieberman, Judy
Affilliation
Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA / Harvard Medical School. Department of Pediatrics. Boston, MA, USA / Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA / Harvard Medical School. Department of Pediatrics. Boston, MA, USA.
Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA / Harvard Medical School. Department of Pediatrics. Boston, MA, USA.
Harvard Medical School. Department of Pediatrics. Boston, MA, USA / Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Harvard Medical School. Department of Pediatrics. Boston, MA, USA.
Harvard Medical School. Department of Pediatrics. Boston, MA, USA.
Massachusetts General Hospital Institute for Patient Care. Emergency Medicine. Boston, MA, USA.
Harvard Medical School. Department of Pediatrics. Boston, MA, USA.
Harvard Medical School. Blavatnik Institute. Department of Microbiology. Boston, MA, USA.
Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA / Harvard Medical School. Department of Pediatrics. Boston, MA, USA.
Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA / Harvard Medical School. Department of Pediatrics. Boston, MA, USA.
Massachusetts General Hospital Institute for Patient Care. Emergency Medicine. Boston, MA, USA.
Massachusetts General Hospital Institute for Patient Care. Emergency Medicine. Boston, MA, USA.
Massachusetts General Hospital Institute for Patient Care. Emergency Medicine. Boston, MA, USA.
Massachusetts General Hospital Institute for Patient Care. Emergency Medicine. Boston, MA, USA.
Harvard Medical School. Massachusetts Institute of Technology. Massachusetts General Hospital. Ragon Institute. Cambridge, MA, USA.
Harvard Medical School. Massachusetts Institute of Technology. Massachusetts General Hospital. Ragon Institute. Cambridge, MA, USA.
Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA / Harvard Medical School. Department of Biological Chemistry and Molecular Pharmacology. Boston, MA, USA.
Massachusetts Institute of Technology. Institute for Medical Engineering and Science. Cambridge, MA, USA.
Harvard Medical School. Blavatnik Institute. Department of Microbiology. Boston, MA, USA / Massachusetts Institute of Technology. Institute for Medical Engineering and Science. Cambridge, MA, USA.
Harvard Medical School. Department of Pediatrics. Boston, MA, USA / Boston Children's Hospital. Division of Immunology. Boston, MA, USA.
Harvard Medical School. Department of Pediatrics. Boston, MA, USA / Boston Children's Hospital. Division of Immunology. Boston, MA, USA.
Harvard Medical School. Massachusetts Institute of Technology. Massachusetts General Hospital. Ragon Institute. Cambridge, MA, USA.
Harvard Medical School. Dana-Farber Cancer Institute and Department of Cell Biology. cBio Center. Boston, MA, USA.
Harvard Medical School. Blavatnik Institute. Department of Microbiology. Boston, MA, USA.
Harvard Medical School. Blavatnik Institute. Department of Microbiology. Boston, MA, USA / Massachusetts General Hospital. Division of Infectious Diseases. Department of Medicine. Center for Bacterial Pathogenesis. Boston, MA, USA.
Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA / Harvard Medical School. Department of Pediatrics. Boston, MA, USA / Massachusetts Institute of Technology. Institute for Medical Engineering and Science. Cambridge, MA, USA.
University College London. Institute for Liver and Digestive Health. London, UK / Foundation for Liver Research. Institute of Hepatology. London, UK.
University of Cambridge. Department of Clinical Neurosciences. Cambridge, UK.
Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA.
Massachusetts General Hospital Institute for Patient Care. Emergency Medicine. Boston, MA, USA.
Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA / Harvard Medical School. Department of Pediatrics. Boston, MA, USA.
Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA / Harvard Medical School. Department of Pediatrics. Boston, MA, USA.
Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA / Harvard Medical School. Department of Pediatrics. Boston, MA, USA.
Harvard Medical School. Department of Pediatrics. Boston, MA, USA / Fundação Oswaldo Cruz. Instituto René Rachou. Belo Horizonte, MG, Brasil.
Harvard Medical School. Department of Pediatrics. Boston, MA, USA.
Harvard Medical School. Department of Pediatrics. Boston, MA, USA.
Massachusetts General Hospital Institute for Patient Care. Emergency Medicine. Boston, MA, USA.
Harvard Medical School. Department of Pediatrics. Boston, MA, USA.
Harvard Medical School. Blavatnik Institute. Department of Microbiology. Boston, MA, USA.
Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA / Harvard Medical School. Department of Pediatrics. Boston, MA, USA.
Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA / Harvard Medical School. Department of Pediatrics. Boston, MA, USA.
Massachusetts General Hospital Institute for Patient Care. Emergency Medicine. Boston, MA, USA.
Massachusetts General Hospital Institute for Patient Care. Emergency Medicine. Boston, MA, USA.
Massachusetts General Hospital Institute for Patient Care. Emergency Medicine. Boston, MA, USA.
Massachusetts General Hospital Institute for Patient Care. Emergency Medicine. Boston, MA, USA.
Harvard Medical School. Massachusetts Institute of Technology. Massachusetts General Hospital. Ragon Institute. Cambridge, MA, USA.
Harvard Medical School. Massachusetts Institute of Technology. Massachusetts General Hospital. Ragon Institute. Cambridge, MA, USA.
Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA / Harvard Medical School. Department of Biological Chemistry and Molecular Pharmacology. Boston, MA, USA.
Massachusetts Institute of Technology. Institute for Medical Engineering and Science. Cambridge, MA, USA.
Harvard Medical School. Blavatnik Institute. Department of Microbiology. Boston, MA, USA / Massachusetts Institute of Technology. Institute for Medical Engineering and Science. Cambridge, MA, USA.
Harvard Medical School. Department of Pediatrics. Boston, MA, USA / Boston Children's Hospital. Division of Immunology. Boston, MA, USA.
Harvard Medical School. Department of Pediatrics. Boston, MA, USA / Boston Children's Hospital. Division of Immunology. Boston, MA, USA.
Harvard Medical School. Massachusetts Institute of Technology. Massachusetts General Hospital. Ragon Institute. Cambridge, MA, USA.
Harvard Medical School. Dana-Farber Cancer Institute and Department of Cell Biology. cBio Center. Boston, MA, USA.
Harvard Medical School. Blavatnik Institute. Department of Microbiology. Boston, MA, USA.
Harvard Medical School. Blavatnik Institute. Department of Microbiology. Boston, MA, USA / Massachusetts General Hospital. Division of Infectious Diseases. Department of Medicine. Center for Bacterial Pathogenesis. Boston, MA, USA.
Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA / Harvard Medical School. Department of Pediatrics. Boston, MA, USA / Massachusetts Institute of Technology. Institute for Medical Engineering and Science. Cambridge, MA, USA.
University College London. Institute for Liver and Digestive Health. London, UK / Foundation for Liver Research. Institute of Hepatology. London, UK.
University of Cambridge. Department of Clinical Neurosciences. Cambridge, UK.
Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA / Harvard Medical School. Department of Medicine. Boston, MA, USA.
Massachusetts General Hospital Institute for Patient Care. Emergency Medicine. Boston, MA, USA.
Boston Children's Hospital. Program in Cellular and Molecular Medicine. Boston, MA, USA / Harvard Medical School. Department of Pediatrics. Boston, MA, USA.
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.
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