Sirtuin-dependent metabolic and epigenetic regulation of macrophages during tuberculosis

被引:10
作者
Zhang, Kangling [1 ]
Sowers, Mark L. [1 ]
Cherryhomes, Ellie I. [1 ]
Singh, Vipul K. [2 ]
Mishra, Abhishek [2 ]
Restrepo, Blanca I. [3 ]
Khan, Arshad [2 ]
Jagannath, Chinnaswamy [2 ]
机构
[1] Univ Texas Med Branch, Dept Pharmacol & Toxicol, Galveston, TX 77555 USA
[2] Houston Methodist Res Inst, Weill Cornell Med, Dept Pathol & Genom Med, Houston, TX 77030 USA
[3] Univ Texas Hlth Houston, Sch Publ Hlth, Brownsville, TX USA
来源
FRONTIERS IN IMMUNOLOGY | 2023年 / 14卷
关键词
human macrophages; autophagy; glycolysis; metabolism; histone modifications; SIRTUIN; ATP-CITRATE LYASE; NITRIC-OXIDE SYNTHASE; QUINOLINIC ACID PHOSPHORIBOSYLTRANSFERASE; ELECTRON-TRANSPORT CHAIN; MYCOBACTERIUM-TUBERCULOSIS; HISTONE ACETYLATION; CALORIE RESTRICTION; PYRUVATE-KINASE; PROTEIN ACETYLATION; INDUCED AUTOPHAGY;
D O I
10.3389/fimmu.2023.1121495
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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.
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页数:20
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