Decitabine Promotes Modulation in Phenotype and Function of Monocytes and Macrophages That Drive Immune Response Regulation

Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of dec...

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Bibliographic Details
Published in:Cells (Basel, Switzerland) Switzerland), 2021-04, Vol.10 (4), p.868
Main Authors: Zambuzi, Fabiana Albani, Cardoso-Silva, Priscilla Mariane, Castro, Ricardo Cardoso, Fontanari, Caroline, Emery, Flavio da Silva, Frantz, Fabiani Gai
Format: Article
Language:English
Subjects:
5-aza-2'-deoxycytidine
Bacteria
Cytokines
DNA methylation
DNMT inhibitors
Epigenetics
Flow cytometry
Granulomas
IL-1β
immune cell
Immune response
Immunomodulation
Immunoregulation
Infections
Infectious diseases
Inflammation
Innate immunity
Interleukin 10
Interleukin 8
Lymphocytes
Macrophages
Metabolism
Metabolites
Microbicides
monocyte/macrophages
Monocytes
Pathogens
Phagocytosis
Phenotypes
Tuberculosis
Tumor necrosis factor-α
γ-Interferon
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Summary:Decitabine is an approved hypomethylating agent used for treating hematological malignancies. Although decitabine targets altered cells, epidrugs can trigger immunomodulatory effects, reinforcing the hypothesis of immunoregulation in treated patients. We therefore aimed to evaluate the impact of decitabine treatment on the phenotype and functions of monocytes and macrophages, which are pivotal cells of the innate immunity system. In vitro decitabine administration increased bacterial phagocytosis and IL-8 release, but impaired microbicidal activity of monocytes. In addition, during monocyte-to-macrophage differentiation, treatment promoted the M2-like profile, with increased expression of CD206 and ALOX15. Macrophages also demonstrated reduced infection control when exposed to in vitro. However, cytokine production remained unchanged, indicating an atypical M2 macrophage. Furthermore, when macrophages were cocultured with lymphocytes, decitabine induced a reduction in the release of inflammatory cytokines such as IL-1β, TNF-α, and IFN-γ, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response.
ISSN:2073-4409
2073-4409
DOI:10.3390/cells10040868