Metabolic Reprogramming in Innate Immune Cell Fate and Function

A special issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: closed (1 December 2019) | Viewed by 57868

Special Issue Editor


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Guest Editor
CASE School of Medicine, 2103 Cornell Road, Cleveland, OH 44106, USA
Interests: innate immunity; macrophages; innate lymphoid cells; immunometabolism
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Special Issue Information

Dear Colleagues,

The field of immunometabolism is an interdisciplinary work between metabolism and immunology research. There is no doubt that immune cell fate and function are intimately linked to metabolic regulations. Meanwhile, inflammation can drive metabolic alterations/disorders to modulate immune cell differentiation and activation.

In this Special Issue, we will focus on how regulatory circuits and nutrients in lipid and mitochondria, carbohydrate and amino acid metabolism, mTOR signaling, autophagy, and endoplasmic reticulum (ER) stress responses shape and fine-tune the differentiation, activation, and effector function of innate immune cells. Additionally, this issue will provide an updated overview on metabolic reprogramming in macrophages, myeloid-derived suppressor cells, dendritic cells, NK/innate lymphoid cells, and B cell humoral immunity in inflammatory microenvironments, such as cancer, infection, atherosclerosis, and obesity.

Molecular and genetic analyses of the immune system have made it clear that immune cells eliminate pathogenic intruders and maintain tissue homeostasis through a complex network of intrinsic and extrinsic signaling and metabolism. Given the complexity of our immune system, systems biology has provided us with informative readouts in changes of single-cell resolution, molecular omics, and chromatin modification. Thus, we will discuss directions and challenges in systems immunometabolism, as single-cell global profiling will continue to define novel states of immune cells associated with healthy and diseased individuals.

Dr. Stanley Huang
Guest Editor

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Keywords

  • immunometabolism
  • metabolic reprogramming
  • innate immunity
  • immune cell activation
  • inflammatory microenvironment
  • systems immunology

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Published Papers (7 papers)

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Research

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10 pages, 1067 KiB  
Article
Glycogen Metabolism Supports Early Glycolytic Reprogramming and Activation in Dendritic Cells in Response to Both TLR and Syk-Dependent CLR Agonists
by Kylie D. Curtis, Portia R. Smith, Hannah W. Despres, Julia P. Snyder, Tyler C. Hogan, Princess D. Rodriguez and Eyal Amiel
Cells 2020, 9(3), 715; https://doi.org/10.3390/cells9030715 - 14 Mar 2020
Cited by 13 | Viewed by 3684
Abstract
Dendritic cells (DCs) increase their metabolic dependence on glucose and glycolysis to support their maturation, activation-associated cytokine production, and T-cell stimulatory capacity. We have previously shown that this increase in glucose metabolism can be initiated by both Toll-like receptor (TLR) and C-type lectin [...] Read more.
Dendritic cells (DCs) increase their metabolic dependence on glucose and glycolysis to support their maturation, activation-associated cytokine production, and T-cell stimulatory capacity. We have previously shown that this increase in glucose metabolism can be initiated by both Toll-like receptor (TLR) and C-type lectin receptor (CLR) agonists. In addition, we have shown that the TLR-dependent demand for glucose is partially satisfied by intracellular glycogen stores. However, the role of glycogen metabolism in supporting CLR-dependent DC glycolytic demand has not been formally demonstrated. In this work, we have shown that DCs activated with fungal-associated β-glucan ligands exhibit acute glycolysis induction that is dependent on glycogen metabolism. Furthermore, glycogen metabolism supports DC maturation, inflammatory cytokine production, and priming of the nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome in response to both TLR- and CLR-mediated activation. These data support a model in which different classes of innate immune receptors functionally converge in their requirement for glycogen-dependent glycolysis to metabolically support early DC activation. These studies provide new insight into how DC immune effector function is metabolically regulated in response to diverse inflammatory stimuli. Full article
(This article belongs to the Special Issue Metabolic Reprogramming in Innate Immune Cell Fate and Function)
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Review

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11 pages, 993 KiB  
Review
ER Stress Responses: An Emerging Modulator for Innate Immunity
by Giusy Di Conza and Ping-Chih Ho
Cells 2020, 9(3), 695; https://doi.org/10.3390/cells9030695 - 12 Mar 2020
Cited by 156 | Viewed by 11767
Abstract
The endoplasmic reticulum (ER) is a critical organelle, storing the majority of calcium and governing protein translation. Thus, it is crucial to keep the homeostasis in all ER components and machineries. The ER stress sensor pathways, including IRE1/sXBP1, PERK/EIf2α and ATF6, orchestrate the [...] Read more.
The endoplasmic reticulum (ER) is a critical organelle, storing the majority of calcium and governing protein translation. Thus, it is crucial to keep the homeostasis in all ER components and machineries. The ER stress sensor pathways, including IRE1/sXBP1, PERK/EIf2α and ATF6, orchestrate the major regulatory circuits to ensure ER homeostasis. The embryonic or postnatal lethality that occurs upon genetic depletion of these sensors reveals the essential role of the ER stress pathway in cell biology. In contrast, the impairment or excessive activation of ER stress has been reported to cause or aggravate several diseases such as atherosclerosis, diabetes, NAFDL/NASH, obesity and cancer. Being part of innate immunity, myeloid cells are the first immune cells entering the inflammation site. Upon entry into a metabolically stressed disease environment, activation of ER stress occurs within the myeloid compartment, leading to the modulation of their phenotype and functions. In this review, we discuss causes and consequences of ER stress activation in the myeloid compartment with a special focus on the crosstalk between ER, innate signaling and metabolic environments. Full article
(This article belongs to the Special Issue Metabolic Reprogramming in Innate Immune Cell Fate and Function)
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22 pages, 1470 KiB  
Review
Carbohydrate and Amino Acid Metabolism as Hallmarks for Innate Immune Cell Activation and Function
by Haoxin Zhao, Lydia N. Raines and Stanley Ching-Cheng Huang
Cells 2020, 9(3), 562; https://doi.org/10.3390/cells9030562 - 27 Feb 2020
Cited by 32 | Viewed by 14019
Abstract
Immune activation is now understood to be fundamentally linked to intrinsic and/or extrinsic metabolic processes which are essential for immune cells to survive, proliferate, and perform their effector functions. Moreover, disruption or dysregulation of these pathways can result in detrimental outcomes and underly [...] Read more.
Immune activation is now understood to be fundamentally linked to intrinsic and/or extrinsic metabolic processes which are essential for immune cells to survive, proliferate, and perform their effector functions. Moreover, disruption or dysregulation of these pathways can result in detrimental outcomes and underly a number of pathologies in both communicable and non-communicable diseases. In this review, we discuss how the metabolism of carbohydrates and amino acids in particular can modulate innate immunity and how perturbations in these pathways can result in failure of these immune cells to properly function or induce unfavorable phenotypes. Full article
(This article belongs to the Special Issue Metabolic Reprogramming in Innate Immune Cell Fate and Function)
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0 pages, 1025 KiB  
Review
RETRACTED: Living with Yourself: Innate Lymphoid Cell Immunometabolism
by Marion Rolot and Timothy E. O’Sullivan
Cells 2020, 9(2), 334; https://doi.org/10.3390/cells9020334 - 1 Feb 2020
Cited by 13 | Viewed by 4134 | Retraction
Abstract
Innate lymphoid cells (ILCs) are tissue-resident sentinels of the immune system that function to protect local tissue microenvironments against pathogens and maintain homeostasis. However, because ILCs are sensitively tuned to perturbations within tissues, they can also contribute to host pathology when critical activating [...] Read more.
Innate lymphoid cells (ILCs) are tissue-resident sentinels of the immune system that function to protect local tissue microenvironments against pathogens and maintain homeostasis. However, because ILCs are sensitively tuned to perturbations within tissues, they can also contribute to host pathology when critical activating signals become dysregulated. Recent work has demonstrated that the crosstalk between ILCs and their environment has a significant impact on host metabolism in health and disease. In this review, we summarize studies that support evidence for the ability of ILCs to influence tissue and systemic metabolism, as well as how ILCs can be regulated by environmental changes in systemic host metabolism. We also highlight studies demonstrating how ILC- intrinsic metabolism influences their activation, proliferation, and homeostasis. Finally, this review discusses the challenges and open questions in the rapidly expanding field of ILCs and immunometabolism. Full article
(This article belongs to the Special Issue Metabolic Reprogramming in Innate Immune Cell Fate and Function)
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23 pages, 1841 KiB  
Review
Pathogens MenTORing Macrophages and Dendritic Cells: Manipulation of mTOR and Cellular Metabolism to Promote Immune Escape
by Lonneke V. Nouwen and Bart Everts
Cells 2020, 9(1), 161; https://doi.org/10.3390/cells9010161 - 9 Jan 2020
Cited by 25 | Viewed by 6892
Abstract
Myeloid cells, including macrophages and dendritic cells, represent an important first line of defense against infections. Upon recognition of pathogens, these cells undergo a metabolic reprogramming that supports their activation and ability to respond to the invading pathogens. An important metabolic regulator of [...] Read more.
Myeloid cells, including macrophages and dendritic cells, represent an important first line of defense against infections. Upon recognition of pathogens, these cells undergo a metabolic reprogramming that supports their activation and ability to respond to the invading pathogens. An important metabolic regulator of these cells is mammalian target of rapamycin (mTOR). During infection, pathogens use host metabolic pathways to scavenge host nutrients, as well as target metabolic pathways for subversion of the host immune response that together facilitate pathogen survival. Given the pivotal role of mTOR in controlling metabolism and DC and macrophage function, pathogens have evolved strategies to target this pathway to manipulate these cells. This review seeks to discuss the most recent insights into how pathogens target DC and macrophage metabolism to subvert potential deleterious immune responses against them, by focusing on the metabolic pathways that are known to regulate and to be regulated by mTOR signaling including amino acid, lipid and carbohydrate metabolism, and autophagy. Full article
(This article belongs to the Special Issue Metabolic Reprogramming in Innate Immune Cell Fate and Function)
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17 pages, 1205 KiB  
Review
Metabolic Reprogramming in Mitochondria of Myeloid Cells
by Hao Zuo and Yihong Wan
Cells 2020, 9(1), 5; https://doi.org/10.3390/cells9010005 - 18 Dec 2019
Cited by 38 | Viewed by 7601
Abstract
The myeloid lineage consists of multiple immune cell types, such as macrophages, monocytes, and dendritic cells. It actively participates in both innate and adaptive immunity. In response to pro- or anti-inflammatory signals, these cells undergo distinct programmed metabolic changes especially in mitochondria. Pro-inflammatory [...] Read more.
The myeloid lineage consists of multiple immune cell types, such as macrophages, monocytes, and dendritic cells. It actively participates in both innate and adaptive immunity. In response to pro- or anti-inflammatory signals, these cells undergo distinct programmed metabolic changes especially in mitochondria. Pro-inflammatory signals induce not only a simple shift from oxidative phosphorylation to glycolysis, but also complicated metabolic alterations during the early and tolerant stages in myeloid cells. In mitochondria, a broken Krebs cycle leads to the accumulation of two metabolites, citrate and succinate, both of which trigger pro-inflammatory responses of myeloid cells. A deficient electron transport chain induces pro-inflammatory responses in the resting myeloid cells while it suppresses these responses in the polarized cells during inflammation. The metabolic reprogramming in mitochondria is also associated with altered mitochondrial morphology. On the other hand, intact oxidative phosphorylation is required for the anti-inflammatory functions of myeloid cells. Fatty acid synthesis is essential for the pro-inflammatory effect and glutamine metabolism in mitochondria exhibits the anti-inflammatory effect. A few aspects of metabolic reprogramming remain uncertain, for example, glycolysis and fatty acid oxidation in anti-inflammation. Overall, metabolic reprogramming is an important element of immune responses in myeloid cells. Full article
(This article belongs to the Special Issue Metabolic Reprogramming in Innate Immune Cell Fate and Function)
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15 pages, 690 KiB  
Review
Shaping of Innate Immune Response by Fatty Acid Metabolite Palmitate
by Hong-Tai Tzeng, I-Tsu Chyuan and Wei-Yu Chen
Cells 2019, 8(12), 1633; https://doi.org/10.3390/cells8121633 - 13 Dec 2019
Cited by 33 | Viewed by 8573
Abstract
Innate immune cells monitor invading pathogens and pose the first-line inflammatory response to coordinate with adaptive immunity for infection removal. Innate immunity also plays pivotal roles in injury-induced tissue remodeling and the maintenance of tissue homeostasis in physiological and pathological conditions. Lipid metabolites [...] Read more.
Innate immune cells monitor invading pathogens and pose the first-line inflammatory response to coordinate with adaptive immunity for infection removal. Innate immunity also plays pivotal roles in injury-induced tissue remodeling and the maintenance of tissue homeostasis in physiological and pathological conditions. Lipid metabolites are emerging as the key players in the regulation of innate immune responses, and recent work has highlighted the importance of the lipid metabolite palmitate as an essential component in this regulation. Palmitate modulates innate immunity not only by regulating the activation of pattern recognition receptors in local innate immune cells, but also via coordinating immunological activity in inflammatory tissues. Moreover, protein palmitoylation controls various cellular physiological processes. Herein, we review the updated evidence that palmitate catabolism contributes to innate immune cell-mediated inflammatory processes that result in immunometabolic disorders. Full article
(This article belongs to the Special Issue Metabolic Reprogramming in Innate Immune Cell Fate and Function)
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