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

Author(s)

Zambuzi, Fabiana Albani ^{[1, 2]} ; Cardoso-Silva, Priscilla Mariane ^[1] ; Castro, Ricardo Cardoso ^[1] ; Fontanari, Caroline ^[1] ; Emery, Flavio da Silva ^[1] ; Frantz, Fabiani Gai ^[1]

Affiliation

^[1] Univ Sao Paulo, Fac Ciencias Farmaceut Ribeirao Preto FCFRP, BR-14041903 Ribeirao Preto, SP - Brazil

^[2] Fac Ciencias Saude Barretos Dr Paulo Prata FACISB, BR-14785002 Barretos, SP - Brazil

• Document type: Journal article
• Source: CELLS; v. 10, n. 4 APR 2021.
• Web of Science Citations: 0

Abstract

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 Mycobacterium tuberculosis 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-1 beta, TNF-alpha, and IFN-gamma, maintaining IL-10 production, suggesting that decitabine could potentialize M2 polarization and might be considered as a therapeutic against the exacerbated immune response. (AU)

• FAPESP's process: 18/15066-0 - Epigenetic programming during chronic infectious diseases: tiring out and training the innate immune system
• Grantee: Fabiani Gai Frantz
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 17/05365-8 - Functional biomarkers of the immune response in human tuberculosis
• Grantee: Fabiani Gai Frantz
• Support Opportunities: Regular Research Grants