Multi-OMICs analysis reveals metabolic and epigenetic changes associated with macrophage polarization

Sowers, Mark L.; Tang, Hui; Singh, Vipul K.; Khan, Arshad; Mishra, Abhishek; Restrepo, Blanca I.; Jagannath, Chinnaswamy; Zhang, Kangling

doi:10.1016/j.jbc.2022.102418

Cited by 13 publications

(21 citation statements)

References 80 publications

(87 reference statements)

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“…However, as the infection progresses to 24 and 48 hr, post-infection, the M1- metabolic state of macrophages is reversed and an increase in TCA cycle and oxidative phosphorylation with dampened glycolysis are observed suggesting a switch towards M2-MΦs ( 9 , 81 , 85 ). These data are consistent with increased glycolysis and reduced TCA proteins in human M1-MΦs and switch towards M2-MΦs observed using proteomics analysis in our lab ( 86 ). Whereas most proteins of the ETC complexes II-IV were down-regulated, majority of proteins in complex I were up-regulated in human M1-MΦs ( 86 ).…”

Section: Metabolic Profiles Of Mouse and Human M1- Versus M2-mφs Duri...supporting

confidence: 90%

“…These data are consistent with increased glycolysis and reduced TCA proteins in human M1-MΦs and switch towards M2-MΦs observed using proteomics analysis in our lab ( 86 ). Whereas most proteins of the ETC complexes II-IV were down-regulated, majority of proteins in complex I were up-regulated in human M1-MΦs ( 86 ).…”

Section: Metabolic Profiles Of Mouse and Human M1- Versus M2-mφs Duri...supporting

confidence: 90%

“…Although many metabolic profiling studies have been done using mouse macrophages, recent studies are focusing on human macrophages ( 86 – 92 ). For example, mice are more susceptible to tuberculosis whereas nearly 90% of humans exposed to tuberculosis develop latent infection indicating a better control by their macrophages.…”

Section: Metabolic Profiles Of Mouse and Human M1- Versus M2-mφs Duri...mentioning

confidence: 99%

“…In this direction, we measured mRNA expression of SIRT5 which was significantly higher in MTB-infected and uninfected M1-MФs than in M2-MФs cultured under identical conditions ( 6 ). Because we had detected that a majority of the proteins in the ETC complex I in M1-MФs was up-regulated ( 86 ), we suspected that not only desuccinylation by SIRT5 but also protein expression of ETC complex I promote NADH oxidation into NAD + and ROS in M1-MФs. We also found an inverse relationship between acetylated amino acids and acetylated histones ( 86 ).…”

Section: Sirtuins and Nad + Regulate Protein/histo...mentioning

confidence: 99%

“…Because we had detected that a majority of the proteins in the ETC complex I in M1-MФs was up-regulated ( 86 ), we suspected that not only desuccinylation by SIRT5 but also protein expression of ETC complex I promote NADH oxidation into NAD + and ROS in M1-MФs. We also found an inverse relationship between acetylated amino acids and acetylated histones ( 86 ). Therefore, we speculated that acetylation of amino acids and acetylation of histones might compete for ac-CoA to fulfill acetylation; in M1-MФs, glycolysis generated acetyl-CoA cannot enter the partially blocked TCA cycle but is consumed by acetylation of amino acids as a consequence of which, the supply of ac-CoA for acetylation of histones is diminished.…”

Section: Sirtuins and Nad + Regulate Protein/histo...mentioning

confidence: 99%

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Sirtuin-dependent metabolic and epigenetic regulation of macrophages during tuberculosis

et al. 2023

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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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Section: Metabolic Profiles Of Mouse and Human M1- Versus M2-mφs Duri...supporting

confidence: 90%

Section: Metabolic Profiles Of Mouse and Human M1- Versus M2-mφs Duri...supporting

confidence: 90%

Section: Metabolic Profiles Of Mouse and Human M1- Versus M2-mφs Duri...mentioning

confidence: 99%

Section: Sirtuins and Nad + Regulate Protein/histo...mentioning

confidence: 99%

Section: Sirtuins and Nad + Regulate Protein/histo...mentioning

confidence: 99%

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Sirtuin-dependent metabolic and epigenetic regulation of macrophages during tuberculosis

et al. 2023

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Stimuli‐Mediated Macrophage Switching, Unraveling the Dynamics at the Nanoplatforms–Macrophage Interface

Ganguly,

Luthfikasari,

Randhawa

et al. 2024

Adv Healthcare Materials

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Macrophages play an essential role in immunotherapy and tissue regeneration owing to their remarkable plasticity and diverse functions. Recent bioengineering developments have focused on using external physical stimuli such as electric and magnetic fields, temperature, and compressive stress, among others, on micro/nanostructures to induce macrophage polarization, thereby increasing their therapeutic potential. However, it is difficult to find a concise review of the interaction between physical stimuli, advanced micro/nanostructures, and macrophage polarization. This review examines the present research on physical stimuli‐induced macrophage polarization on micro/nanoplatforms, emphasizing the synergistic role of fabricated structure and stimulation for advanced immunotherapy and tissue regeneration. We provide a concise overview of the research advancements investigating the impact of physical stimuli‐including electric fields, magnetic fields, compressive forces, fluid shear stress, photothermal stimuli, and multiple stimulations on the polarization of macrophages within complex engineered structures. The prospective implications of these strategies in regenerative medicine and immunotherapeutic approaches have been highlighted. This review will aid in creating stimuli‐responsive platforms for immunomodulation and tissue regeneration.This article is protected by copyright. All rights reserved

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The vitamin B5/coenzyme A axis: A target for immunomodulation?

et al. 2023

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Coenzyme A (CoA) serves as a vital cofactor in numerous enzymatic reactions involved in energy production, lipid metabolism, and synthesis of essential molecules. Dysregulation of CoA‐dependent metabolic pathways can contribute to chronic diseases, such as inflammatory diseases, obesity, diabetes, cancer, and cardiovascular disorders. Additionally, CoA influences immune cell activation by modulating the metabolism of these cells, thereby affecting their proliferation, differentiation, and effector functions. Targeting CoA metabolism presents a promising avenue for therapeutic intervention, as it can potentially restore metabolic balance, mitigate chronic inflammation, and enhance immune cell function. This might ultimately improve the management and outcomes for these diseases. This review will more specifically focus on the contribution of pathways regulating the availability of the CoA precursor Vitamin B5/pantothenate in vivo and modulating the development of Th17‐mediated inflammation, CD8‐dependent anti‐tumor immunity but also tissue repair processes in chronic inflammatory or degenerative diseases.

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Multi-OMICs analysis reveals metabolic and epigenetic changes associated with macrophage polarization

Cited by 13 publications

References 80 publications

Sirtuin-dependent metabolic and epigenetic regulation of macrophages during tuberculosis

Sirtuin-dependent metabolic and epigenetic regulation of macrophages during tuberculosis

Stimuli‐Mediated Macrophage Switching, Unraveling the Dynamics at the Nanoplatforms–Macrophage Interface

The vitamin B5/coenzyme A axis: A target for immunomodulation?

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