TY - JOUR TI - Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells AU - Salina, Ana CG AU - dos-Santos, Douglas AU - Rodrigues, Tamara S AU - Fortes-Rocha, Marlon AU - Freitas-Filho, Edismauro G AU - Alzamora-Terrel, Daniel L AU - Castro, Icaro MS AU - Fraga da Silva, Thais FC AU - de Lima, Mikhael HF AU - Nascimento, Daniele C AU - Silva, Camila M AU - Toller-Kawahisa, Juliana E AU - Becerra, Amanda AU - Oliveira, Samuel AU - Caetité, Diego B AU - Almeida, Leticia AU - Ishimoto, Adriene Y AU - Lima, Thais M AU - Martins, Ronaldo B AU - Veras, Flavio AU - do Amaral, Natália B AU - Giannini, Marcela C AU - Bonjorno, Letícia P AU - Lopes, Maria IF AU - Benatti, Maira N AU - Batah, Sabrina S AU - Santana, Rodrigo C AU - Vilar, Fernando C AU - Martins, Maria A AU - Assad, Rodrigo L AU - de Almeida, Sergio CL AU - de Oliveira, Fabiola R AU - Arruda Neto, Eurico AU - Cunha, Thiago M AU - Alves-Filho, José C AU - Bonato, Vania LD AU - Cunha, Fernando Q AU - Fabro, Alexandre T AU - Nakaya, Helder I AU - Zamboni, Dario S AU - Louzada-Junior, Paulo AU - Oliveira, Rene DR AU - Cunha, Larissa D A2 - Sigal, Alex A2 - Rothlin, Carla V A2 - Sugimura, Rio VL - 11 PY - 2022 DA - 2022/06/06 SP - e74443 C1 - eLife 2022;11:e74443 DO - 10.7554/eLife.74443 UR - https://doi.org/10.7554/eLife.74443 AB - 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. KW - COVID-19 KW - SARS-CoV-2 KW - macrophage polarization KW - efferocytosis KW - hyperinflammation KW - tissue repair JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -