Abstract
Macrophages are the preeminent phagocytic cells which control multiple infections. Tuberculosis a leading cause of death in mankind and the causative organism Mycobacterium tuberculosis (MTB) infects and persists in macrophages. Macrophages use reactive oxygen and nitrogen species (ROS/RNS) and autophagy to kill and degrade microbes including MTB. Glucose metabolism regulates the macrophage-mediated antimicrobial mechanisms. Whereas glucose is essential for the growth of cells in immune cells, glucose metabolism and its downsteam metabolic pathways generate key mediators which are essential co-substrates for post-translational modifications of histone proteins, which in turn, epigenetically regulate gene expression. Herein, we describe the role of sirtuins which are NAD+-dependent histone histone/protein deacetylases during the epigenetic regulation of autophagy, the production of ROS/RNS, acetyl-CoA, NAD+, and S-adenosine methionine (SAM), and illustrate the cross-talk between immunometabolism and epigenetics on macrophage activation. We highlight sirtuins as emerging therapeutic targets for modifying immunometabolism to alter macrophage phenotype and antimicrobial function.
Original language | English (US) |
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Article number | 1121495 |
Pages (from-to) | 1121495 |
Journal | Frontiers in immunology |
Volume | 14 |
DOIs | |
State | Published - 2023 |
Keywords
- SIRTUIN
- autophagy
- glycolysis
- histone modifications
- human macrophages
- metabolism
- Reactive Oxygen Species/metabolism
- Humans
- Epigenesis, Genetic
- Macrophages
- Histones/metabolism
- Sirtuins/genetics
- Tuberculosis
- Anti-Infective Agents/metabolism
- NAD/metabolism
ASJC Scopus subject areas
- Immunology and Allergy
- Immunology