Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells

COVID-19 is a disease of dysfunctional immune responses, but the mechanisms triggering immunopathogenesis are not established. The functional plasticity of macrophages allows this cell type to promote pathogen elimination and inflammation or suppress inflammation and promote tissue remodeling and in...

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Published in:	eLife Vol. 11
Main Authors:	Salina, Ana C G, Dos-Santos, Douglas, Rodrigues, Tamara S, Fortes-Rocha, Marlon, Freitas-Filho, Edismauro G, Alzamora-Terrel, Daniel L, Castro, Icaro M S, Fraga da Silva, Thais F C, de Lima, Mikhael H F, Nascimento, Daniele C, Silva, Camila M, Toller-Kawahisa, Juliana E, Becerra, Amanda, Oliveira, Samuel, Caetité, Diego B, Almeida, Leticia, Ishimoto, Adriene Y, Lima, Thais M, Martins, Ronaldo B, Veras, Flavio, do Amaral, Natália B, Giannini, Marcela C, Bonjorno, Letícia P, Lopes, Maria I F, Benatti, Maira N, Batah, Sabrina S, Santana, Rodrigo C, Vilar, Fernando C, Martins, Maria A, Assad, Rodrigo L, de Almeida, Sergio C L, de Oliveira, Fabiola R, Arruda Neto, Eurico, Cunha, Thiago M, Alves-Filho, José C, Bonato, Vania L D, Cunha, Fernando Q, Fabro, Alexandre T, Nakaya, Helder I, Zamboni, Dario S, Louzada-Junior, Paulo, Oliveira, Rene D R, Cunha, Larissa D
Format:	Journal Article
Language:	English
Published:	England eLife Science Publications, Ltd 06-06-2022 eLife Sciences Publications Ltd eLife Sciences Publications, Ltd
Subjects:	Anti-Inflammatory Agents - pharmacology Anti-inflammatory drugs Apoptosis Coronaviruses COVID-19 Cytokines Cytotoxicity Dehydrogenases Development and progression Disease efferocytosis Flow cytometry Functional plasticity Gene expression Health aspects Homeostasis Humans hyperinflammation Immune clearance Immune response Immunology and Inflammation Immunopathogenesis Infection Infections Inflammation Lungs macrophage polarization Macrophages Macrophages - metabolism Monocytes Phagocytosis SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2 tissue repair COVID-19 SARS-CoV-2 inflammation efferocytosis macrophage polarization human hyperinflammation immunology tissue repair
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Summary:	COVID-19 is a disease of dysfunctional immune responses, but the mechanisms triggering immunopathogenesis are not established. The functional plasticity of macrophages allows this cell type to promote pathogen elimination and inflammation or suppress inflammation and promote tissue remodeling and injury repair. During an infection, the clearance of dead and dying cells, a process named efferocytosis, can modulate the interplay between these contrasting functions. Here, we show that engulfment of SARS-CoV-2-infected apoptotic cells exacerbates inflammatory cytokine production, inhibits the expression of efferocytic receptors, and impairs continual efferocytosis by macrophages. We also provide evidence supporting that lung monocytes and macrophages from severe COVID-19 patients have compromised efferocytic capacity. Our findings reveal that dysfunctional efferocytosis of SARS-CoV-2-infected cell corpses suppresses macrophage anti-inflammation and efficient tissue repair programs and provides mechanistic insights for the excessive production of pro-inflammatory cytokines and accumulation of tissue damage associated with COVID-19 immunopathogenesis.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work.
ISSN:	2050-084X 2050-084X
DOI:	10.7554/eLife.74443