Hydroxychloroquine Inhibits the Trained Innate Immune Response to Interferons.
Cell Rep Med
; 1(9): 100146, 2020 12 22.
Article
em En
| MEDLINE
| ID: mdl-33377122
ABSTRACT
Hydroxychloroquine is being investigated for a potential prophylactic effect in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, but its mechanism of action is poorly understood. Circulating leukocytes from the blood of coronavirus disease 2019 (COVID-19) patients show increased responses to Toll-like receptor ligands, suggestive of trained immunity. By analyzing interferon responses of peripheral blood mononuclear cells from healthy donors conditioned with heat-killed Candida, trained innate immunity can be modeled in vitro. In this model, hydroxychloroquine inhibits the responsiveness of these innate immune cells to virus-like stimuli and interferons. This is associated with a suppression of histone 3 lysine 27 acetylation and histone 3 lysine 4 trimethylation of inflammation-related genes, changes in the cellular lipidome, and decreased expression of interferon-stimulated genes. Our findings indicate that hydroxychloroquine inhibits trained immunity in vitro, which may not be beneficial for the antiviral innate immune response to SARS-CoV-2 infection in patients.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Interferons
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Hidroxicloroquina
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Imunidade Inata
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Memória Imunológica
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Holanda