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

Author(s):Show less -

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.

• Document type: Journal article
• Source: eLIFE; v. 11, p. 24-pg., 2022-06-06.

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. (AU)

• FAPESP's process: 18/25559-4 - Molecular mechanisms of LC3-associated phagocytosis and its role in macrophage function
• Grantee: Larissa Dias da Cunha
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 20/05288-6 - The role of efferocytosis in tissue repair and hyperinflammation in SARS-CoV-2 infection
• Grantee: Larissa Dias da Cunha
• Support Opportunities: Regular Research Grants