| Autor: |
Thais F.C. Fraga-Silva, Ualter G. Cipriano, Marcilio J. Fumagalli, Giseli F. Correa, Carlos A. Fuzo, Douglas dos-Santos, Fabiola L.A.C. Mestriner, Christiane Becari, Andrea Teixeira-Carvalho, Jordana Coelho-dos-Reis, Mayra G. Menegueti, Luiz T.M. Figueiredo, Larissa D. Cunha, Olindo A. Martins-Filho, Marcelo Dias-Baruffi, Maria Auxiliadora-Martins, Rita C. Tostes, Vania L.D. Bonato |
| Jazyk: |
angličtina |
| Rok vydání: |
2023 |
| Předmět: |
|
| Zdroj: |
iScience, Vol 26, Iss 12, Pp 108366- (2023) |
| Druh dokumentu: |
article |
| ISSN: |
2589-0042 |
| DOI: |
10.1016/j.isci.2023.108366 |
| Popis: |
Summary: 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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
|
