A2 Review article, Literature review, Systematic review
Impact of HDAC inhibitors on macrophage polarization to enhance innate immunity against infections (2024)

Faizan, B. M., Srdanović, S., Sundberg, L.-R., Kristín, E. H., Marjomäki, V., & Dekker, F. J. (2024). Impact of HDAC inhibitors on macrophage polarization to enhance innate immunity against infections. Drug Discovery Today, 29(11), Article 104193. https://doi.org/10.1016/j.drudis.2024.104193

JYU authors or editors

Sundberg, Lotta-Riina
Marjomäki, Varpu

Publication details

All authors or editors: Faizan, Bhat Mohammad; Srdanović, Sonja; Sundberg, Lotta-Riina; Kristín, Einarsdóttir Helga; Marjomäki, Varpu; Dekker, Frank J.

Journal or series: Drug Discovery Today

ISSN: 1359-6446

eISSN: 1878-5832

Publication year: 2024

Publication date: 26/09/2024

Volume: 29

Issue number: 11

Article number: 104193

Publisher: Elsevier

Publication country: United Kingdom

Publication language: English

DOI: https://doi.org/10.1016/j.drudis.2024.104193

Publication open access: Openly available

Publication channel open access: Partially open access channel

Publication is parallel published (JYX): https://jyx.jyu.fi/handle/123456789/97613

Abstract

Innate immunity plays an important role in host defense against pathogenic infections. It involves macrophage polarization into either the pro-inflammatory M1 or the anti-inflammatory M2 phenotype, influencing immune stimulation or suppression, respectively. Epigenetic changes during immune reactions contribute to long-term innate immunity imprinting on macrophage polarization. It is becoming increasingly evident that epigenetic modulators, such as histone deacetylase (HDAC) inhibitors (HDACi), enable the enhancement of innate immunity by tailoring macrophage polarization in response to immune stressors. In this review, we summarize current literature on the impact of HDACi and other epigenetic modulators on the functioning of macrophages during diseases that have a strong immune component, such as infections. Depending on the disease context and the chosen therapeutic intervention, HDAC1, HDAC2, HDAC3, HDAC6, or HDAC8 are particularly important in influencing macrophage polarization towards either M1 or M2 phenotypes. We anticipate that therapeutic strategies based on HDAC epigenetic mechanisms will provide a unique approach to boost immunity against disease challenges, including resistant infections.

Keywords: infections; macrophages; inflammation; immune response; immune system; epigenetics; antibiotic resistance