The role of efferocytosis in tissue repair and hyperinflammation in SARS-CoV-2 infection

• Grant number: 20/05288-6
• Support Opportunities: Regular Research Grants
• Start date: July 01, 2020
• End date: June 30, 2023
• Field of knowledge: Biological Sciences - Immunology
• Principal Investigator: Larissa Dias da Cunha
• Grantee: Larissa Dias da Cunha
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Paulo Louzada Junior ; Renê Donizeti Ribeiro de Oliveira
• Associated research grant: 18/25559-4 - Molecular mechanisms of LC3-associated phagocytosis and its role in macrophage function, AP.JP
• Associated scholarship(s): 20/10133-1 - The role of efferocytosis in tissue repair and hyperinflammation in SARS-CoV-2 infection, BP.PD

Abstract

To restrain pathogen growth and to tolerate the negative impact of infection in host fitness are both fundamental requirements to survive an infectious disease. Macrophages are a determinant component of innate immunity during infection, not only to identify, trigger immune responses and eliminate the pathogen but also to restrain the inflammatory response and reduce immunopathology. In the latter process, macrophages are responsible for eliminating dead cells (in a process called efferocytosis) and orchestrating the mechanisms of tissue repair. Patients infected with SARS-CoV-2 that develop severe COVID-19 present symptoms typical of a hyperinflammatory syndrome that causes fatal multiorgan lesions. However, critical patients may have controlled viral loads, suggesting that disruption of tolerance mechanisms and the development of severe immunopathology are at play. The recent reports describing the clinical aspects of COVID-19 indicate the occurrence of exacerbated cell death in the course of infection: patients develop acute lymphopenia and present a high level of markers for inflammatory cell death in their blood. Herein, we hypothesize that excessive cell death during the infection with SARS-CoV-2 and a putative failure in their elimination contribute to the hyperinflammation observed in patients with severe COVID-19. We propose to determine the capacity of phagocytes of COVID-19 patients to eliminate dead cells and to establish the importance of this process for the hyperinflammation and disease severity. Finally, we also aim to investigate a putative biomarker associate with macrophage phagocytic activity that could discriminate against the response of critical COVID-19 patients to immunosuppressive and anti-inflammatory drugs. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

LOPES, MARIA ISABEL; BONJORNO, LETICIA P.; GIANNINI, MARCELA C.; AMARAL, NATALIA B.; MENEZES, PAMELLA INDIRA; DIB, SAULO MUSSE; GIGANTE, SAMARA LIBICH; BENATTI, MAIRA N.; REZEK, UEBE C.; EMRICH-FILHO, LAERTE L.; et al. Beneficial effects of colchicine for moderate to severe COVID-19: a randomised, double-blinded, placebo-controlled clinical trial. RMD OPEN, v. 7, n. 1, 2021. (13/08216-2, 20/05601-6, 20/05288-6, 20/04964-8)

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.; et al. Efferocytosis of SARS-CoV-2-infected dying cells impairs macrophage anti-inflammatory functions and clearance of apoptotic cells. eLIFE, v. 11, p. 24-pg., 2022-06-06. (18/25559-4, 20/05288-6)