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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...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262386/ https://www.ncbi.nlm.nih.gov/pubmed/35666101 http://dx.doi.org/10.7554/eLife.74443 |
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author | Salina, Ana CG dos-Santos, Douglas Rodrigues, Tamara S Fortes-Rocha, Marlon Freitas-Filho, Edismauro G Alzamora-Terrel, Daniel L Castro, Icaro MS Fraga da Silva, Thais FC de Lima, Mikhael HF 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 IF Benatti, Maira N Batah, Sabrina S Santana, Rodrigo C Vilar, Fernando C Martins, Maria A Assad, Rodrigo L de Almeida, Sergio CL de Oliveira, Fabiola R Arruda Neto, Eurico Cunha, Thiago M Alves-Filho, José C Bonato, Vania LD Cunha, Fernando Q Fabro, Alexandre T Nakaya, Helder I Zamboni, Dario S Louzada-Junior, Paulo Oliveira, Rene DR Cunha, Larissa D |
author_facet | Salina, Ana CG dos-Santos, Douglas Rodrigues, Tamara S Fortes-Rocha, Marlon Freitas-Filho, Edismauro G Alzamora-Terrel, Daniel L Castro, Icaro MS Fraga da Silva, Thais FC de Lima, Mikhael HF 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 IF Benatti, Maira N Batah, Sabrina S Santana, Rodrigo C Vilar, Fernando C Martins, Maria A Assad, Rodrigo L de Almeida, Sergio CL de Oliveira, Fabiola R Arruda Neto, Eurico Cunha, Thiago M Alves-Filho, José C Bonato, Vania LD Cunha, Fernando Q Fabro, Alexandre T Nakaya, Helder I Zamboni, Dario S Louzada-Junior, Paulo Oliveira, Rene DR Cunha, Larissa D |
author_sort | Salina, Ana CG |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9262386 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
spelling | pubmed-92623862022-07-08 Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells Salina, Ana CG dos-Santos, Douglas Rodrigues, Tamara S Fortes-Rocha, Marlon Freitas-Filho, Edismauro G Alzamora-Terrel, Daniel L Castro, Icaro MS Fraga da Silva, Thais FC de Lima, Mikhael HF 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 IF Benatti, Maira N Batah, Sabrina S Santana, Rodrigo C Vilar, Fernando C Martins, Maria A Assad, Rodrigo L de Almeida, Sergio CL de Oliveira, Fabiola R Arruda Neto, Eurico Cunha, Thiago M Alves-Filho, José C Bonato, Vania LD Cunha, Fernando Q Fabro, Alexandre T Nakaya, Helder I Zamboni, Dario S Louzada-Junior, Paulo Oliveira, Rene DR Cunha, Larissa D eLife Immunology and Inflammation 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. eLife Sciences Publications, Ltd 2022-06-06 /pmc/articles/PMC9262386/ /pubmed/35666101 http://dx.doi.org/10.7554/eLife.74443 Text en © 2022, Salina, dos-Santos, Rodrigues et al https://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Immunology and Inflammation Salina, Ana CG dos-Santos, Douglas Rodrigues, Tamara S Fortes-Rocha, Marlon Freitas-Filho, Edismauro G Alzamora-Terrel, Daniel L Castro, Icaro MS Fraga da Silva, Thais FC de Lima, Mikhael HF 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 IF Benatti, Maira N Batah, Sabrina S Santana, Rodrigo C Vilar, Fernando C Martins, Maria A Assad, Rodrigo L de Almeida, Sergio CL de Oliveira, Fabiola R Arruda Neto, Eurico Cunha, Thiago M Alves-Filho, José C Bonato, Vania LD Cunha, Fernando Q Fabro, Alexandre T Nakaya, Helder I Zamboni, Dario S Louzada-Junior, Paulo Oliveira, Rene DR Cunha, Larissa D Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells |
title | Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells |
title_full | Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells |
title_fullStr | Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells |
title_full_unstemmed | Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells |
title_short | Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells |
title_sort | efferocytosis of sars-cov-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells |
topic | Immunology and Inflammation |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9262386/ https://www.ncbi.nlm.nih.gov/pubmed/35666101 http://dx.doi.org/10.7554/eLife.74443 |
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