Sirtuin-dependent metabolic and epigenetic regulation of macrophages during tuberculosis. Review uri icon

Overview

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.

publication date

  • March 13, 2023

Research

keywords

  • Anti-Infective Agents
  • Sirtuins
  • Tuberculosis

Identity

PubMed Central ID

  • PMC10040548

Scopus Document Identifier

  • 85150872948

Digital Object Identifier (DOI)

  • 10.3389/fimmu.2023.1121495

PubMed ID

  • 36993975

Additional Document Info

volume

  • 14