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

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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 ; Caetite, Diego B. ; Almeida, Leticia ; Ishimoto, Adriene Y. ; Lima, Thais M. ; Martins, Ronaldo B. ; Veras, Flavio ; do Amaral, Natalia B. ; Giannini, Marcela C. ; Bonjorno, Leticia 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, Jose 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.

• Tipo de documento: Artigo Científico
• Fonte: eLIFE; v. 11, p. 24-pg., 2022-06-06.

Resumo

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. (AU)

• Processo FAPESP: 18/25559-4 - Mecanismos moleculares de fagocitose associada a LC3 e seu papel na regulação da função de macrófagos
• Beneficiário: Larissa Dias da Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
• Processo FAPESP: 20/05288-6 - O papel da eferocitose no dano tecidual e hiperinflamação na infecção por SARS-CoV-2
• Beneficiário: Larissa Dias da Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Regular