Hydroxychloroquine Inhibits the Trained Innate Immune Response to Interferons.
Cell Rep Med
; 1(9): 100146, 2020 12 22.
Article
in English
| MEDLINE | ID: covidwho-917453
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.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Interferons
/
Hydroxychloroquine
/
Immunity, Innate
/
Immunologic Memory
Type of study:
Prognostic study
Limits:
Humans
Language:
English
Journal:
Cell Rep Med
Year:
2020
Document Type:
Article
Affiliation country:
J.xcrm.2020.100146
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