Sirtuin-dependent metabolic and epigenetic regulation of macrophages during tuberculosis

Kangling Zhang, Mark L. Sowers, Ellie I. Cherryhomes, Vipul K. Singh, Abhishek Mishra, Blanca I. Restrepo, Arshad Khan, Chinnaswamy Jagannath

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations


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 languageEnglish (US)
Article number1121495
Pages (from-to)1121495
JournalFrontiers in immunology
StatePublished - Mar 12 2023


  • autophagy
  • glycolysis
  • histone modifications
  • human macrophages
  • metabolism

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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