Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX, United States.
Department of Pathology and Genomic Medicine, Houston Methodist Research Institute, Weill-Cornell Medicine, Houston, TX, United States.
Front Immunol. 2023 Mar 13;14:1121495. doi: 10.3389/fimmu.2023.1121495. eCollection 2023.
Macrophages are the preeminent phagocytic cells which control multiple infections. Tuberculosis a leading cause of death in mankind and the causative organism (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.
巨噬细胞是吞噬细胞中的佼佼者，能够控制多种感染。结核病是人类的主要死因之一，其病原体（MTB）感染并在巨噬细胞中持续存在。巨噬细胞利用活性氧和氮物种（ROS/RNS）和自噬来杀死和降解微生物，包括 MTB。葡萄糖代谢调节巨噬细胞介导的抗菌机制。虽然葡萄糖对于免疫细胞中细胞的生长是必不可少的，但葡萄糖代谢及其下游代谢途径产生的关键介质是组蛋白蛋白/蛋白质去乙酰化酶的必需共底物，组蛋白蛋白/蛋白质去乙酰化酶反过来又通过表观遗传调节基因表达。本文描述了 NAD 依赖性组蛋白/蛋白质去乙酰化酶 sirtuins 在自噬、ROS/RNS、乙酰辅酶 A、NAD 和 S-腺苷甲硫氨酸 (SAM) 的产生过程中的表观遗传调控中的作用，并说明了免疫代谢和表观遗传在巨噬细胞激活中的相互作用。我们强调 sirtuins 是新兴的治疗靶点，可以修饰免疫代谢以改变巨噬细胞表型和抗菌功能。
