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

Authors :
Ana CG Salina
Douglas dos-Santos
Tamara S Rodrigues
Marlon Fortes-Rocha
Edismauro G Freitas-Filho
Daniel L Alzamora-Terrel
Icaro MS Castro
Thais FC Fraga da Silva
Mikhael HF de Lima
Daniele C Nascimento
Camila M Silva
Juliana E Toller-Kawahisa
Amanda Becerra
Samuel Oliveira
Diego B Caetité
Leticia Almeida
Adriene Y Ishimoto
Thais M Lima
Ronaldo B Martins
Flavio Veras
Natália B do Amaral
Marcela C Giannini
Letícia P Bonjorno
Maria IF Lopes
Maira N Benatti
Sabrina S Batah
Rodrigo C Santana
Fernando C Vilar
Maria A Martins
Rodrigo L Assad
Sergio CL de Almeida
Fabiola R de Oliveira
Eurico Arruda Neto
Thiago M Cunha
José C Alves-Filho
Vania LD Bonato
Fernando Q Cunha
Alexandre T Fabro
Helder I Nakaya
Dario S Zamboni
Paulo Louzada-Junior
Rene DR Oliveira
Larissa D Cunha
Source :
eLife, Vol 11 (2022)
Publication Year :
2022
Publisher :
eLife Sciences Publications Ltd, 2022.

Abstract

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.

Details

Language :
English
ISSN :
2050084X
Volume :
11
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.90b9106f59824489a18e93537ba61d8e
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.74443