Hydroxychloroquine Inhibits the Trained Innate Immune Response to Interferons.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 33377122.
- Also identified by DOI 10.1016/j.xcrm.2020.100146 and PMC identifier 7762774.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 <i>Candida</i>, trained innate immunity can be modeled <i>in vitro</i>. 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 <i>in vitro</i>, which may not be beneficial for the antiviral innate immune response to SARS-CoV-2 infection in patients.
Medical subject headings
- Hydroxychloroquine
- Immunity, Innate
- Immunologic Memory
- Interferons