Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2022
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
_version_ 1784742483274498048
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
work_keys_str_mv AT salinaanacg efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT dossantosdouglas efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT rodriguestamaras efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT fortesrochamarlon efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT freitasfilhoedismaurog efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT alzamoraterreldaniell efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT castroicaroms efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT fragadasilvathaisfc efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT delimamikhaelhf efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT nascimentodanielec efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT silvacamilam efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT tollerkawahisajulianae efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT becerraamanda efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT oliveirasamuel efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT caetitediegob efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT almeidaleticia efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT ishimotoadrieney efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT limathaism efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT martinsronaldob efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT verasflavio efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT doamaralnataliab efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT gianninimarcelac efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT bonjornoleticiap efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT lopesmariaif efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT benattimairan efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT batahsabrinas efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT santanarodrigoc efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT vilarfernandoc efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT martinsmariaa efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT assadrodrigol efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT dealmeidasergiocl efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT deoliveirafabiolar efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT arrudanetoeurico efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT cunhathiagom efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT alvesfilhojosec efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT bonatovaniald efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT cunhafernandoq efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT fabroalexandret efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT nakayahelderi efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT zambonidarios efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT louzadajuniorpaulo efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT oliveirarenedr efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells
AT cunhalarissad efferocytosisofsarscov2infecteddyingcellsimpairsmacrophageantiinflammatoryfunctionsandclearanceofapoptoticcells