Author | Fraga-Silva, Thais F C | |
Author | Cipriano, Ualter G | |
Author | Fumagalli, Marcilio J | |
Author | Correa, Giseli F | |
Author | Fuzo, Carlos A | |
Author | Dos-Santos, Douglas | |
Author | Mestriner, Fabiola L A C | |
Author | Becari, Christiane | |
Author | Carvalho, Andrea Teixeira | |
Author | Coelho-Dos-Reis, Jordana | |
Author | Menegueti, Mayra G | |
Author | Figueiredo, Luiz T M | |
Author | Cunha, Larissa Dias | |
Author | Martins Filho, Olindo Assis | |
Author | Dias-Baruffi, Marcelo | |
Author | Auxiliadora-Martins, Maria | |
Author | Tostes, Rita C | |
Author | Bonato, Vania L D | |
Access date | 2024-02-27T17:35:05Z | |
Available date | 2024-02-27T17:35:05Z | |
Document date | 2023 | |
Citation | FRAGA-SILVA, Thais F.C. et al. Airway epithelial cells and macrophages trigger IL-6-CD95/CD95L axis and mediate initial immunopathology of COVID-19. Iscience, v. 26, n. 12, p. 1-18, 2023. Doi: http://dx.doi.org/10.1016/j.isci.2023.108366 | en_US |
URI | https://www.arca.fiocruz.br/handle/icict/62820 | |
Language | eng | en_US |
Publisher | Cell Press | en_US |
Rights | open access | en_US |
Subject in Portuguese | componentes do sistema imune | en_US |
Subject in Portuguese | virologia | en_US |
Title | Airway epithelial cells and macrophages trigger IL-6-CD95/CD95L axis and mediate initial immunopathology of COVID-19 | en_US |
Type | Preprint | en_US |
Abstract | Airway epithelial cells (AEC) infected with SARS-CoV-2 may drive the dysfunction of macrophages during COVID-19. We hypothesized that the direct interaction of AEC with macrophages mediated by CD95/CD95L or indirect interaction mediated by IL-6 signaling are key steps for the COVID-19 severe acute inflammation. The interaction of macrophages with apoptotic and infected AEC increased CD95 and CD163 expression, and induced macrophage death. Macrophages exposed to tracheal aspirate with high IL-6 levels from intubated patients with COVID-19 or to recombinant human IL-6 exhibited decreased HLA-DR expression, increased CD95 and CD163 expression and IL-1β production. IL-6 effects on macrophages were prevented by both CD95/CD95L antagonist and by IL-6 receptor antagonist and IL-6 or CD95 deficient mice showed significant reduction of acute pulmonary inflammation post-infection. Our findings show a non-canonical CD95L-CD95 pathway that simultaneously drives both macrophage activation and dysfunction and point to CD95/CD95L axis as therapeutic target. | en_US |
Affilliation | Department of Biochemistry and Immunology. Ribeirao Preto Medical School. University of Sao Paulo. Ribeirao Preto, SP, Brazil. | en_US |
Affilliation | Basic and Applied Immunology Program. Ribeirao Preto Medical School. University of Sao Paulo. Ribeirao Preto, SP, Brazil. | en_US |
Affilliation | Basic and Applied Immunology Program. Ribeirao Preto Medical School. University of Sao Paulo. Ribeirao Preto, SP, Brazil. | en_US |
Affilliation | Basic and Applied Immunology Program. Ribeirao Preto Medical School. University of Sao Paulo. Ribeirao Preto, SP, Brazil. | en_US |
Affilliation | Department of Clinical Analysis, Toxicology and Food Sciences. School of Pharmaceutical Sciences of Ribeirão Preto. University of Sao Paulo. Ribeirao Preto, SP, Brazil. | en_US |
Affilliation | Department of Cell Biology. Ribeirao Preto Medical School. University of Sao Paulo. Ribeirao Preto, SP, Brazil. | en_US |
Affilliation | Department of Surgery and Anatomy. Ribeirao Preto Medical School. University of Sao Paulo. Ribeirao Preto, SP, Brazil. | en_US |
Affilliation | Department of Surgery and Anatomy. Ribeirao Preto Medical School. University of Sao Paulo. Ribeirao Preto, SP, Brazil. | en_US |
Affilliation | René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of Microbiology. Biological Science Institute. Federal University of Minas Gerais. Belo Horizonte, MG, Brazil. | en_US |
Affilliation | Department of General and Specialized Nursing, Ribeirao Preto Nurse School, University of Sao Paulo. Ribeirao Preto, SP, Brazil. | en_US |
Affilliation | Basic and Applied Immunology Program. Ribeirao Preto Medical School. University of Sao Paulo. Ribeirao Preto, SP, Brazil/Virology Research Center. Ribeirao Preto Medical School. University of Sao Paulo. Ribeirao Preto, SP, Brazil. | en_US |
Affilliation | Department of Cell Biology. Ribeirao Preto Medical School. University of Sao Paulo. Ribeirao Preto, SP, Brazil. | en_US |
Affilliation | René Rachou Institute. Oswaldo Cruz Foundation. Belo Horizonte, MG, Brazil | en_US |
Affilliation | Department of Clinical Analysis, Toxicology and Food Sciences. School of Pharmaceutical Sciences of Ribeirão Preto. University of Sao Paulo. Ribeirao Preto, SP, Brazil. | en_US |
Affilliation | Department of Surgery and Anatomy. Ribeirao Preto Medical School. University of Sao Paulo. Ribeirao Preto, SP, Brazil. | en_US |
Affilliation | Department of Pharmacology. Ribeirao Preto Medical School. University of Sao Paulo. Ribeirao Preto, SP, Brazil. | en_US |
Affilliation | Department of Biochemistry and Immunology. Ribeirao Preto Medical School. University of Sao Paulo. Ribeirao Preto, SP, Brazil/Basic and Applied Immunology Program. Ribeirao Preto Medical School. University of Sao Paulo. Ribeirao Preto, SP, Brazil. | en_US |
Subject | Components of the immune system | en_US |
Subject | Virology | en_US |