scholarly journals Amino acids: key sources for immunometabolites and immunotransmitters

2020 ◽  
Vol 32 (7) ◽  
pp. 435-446 ◽  
Author(s):  
Michio Miyajima
Keyword(s):  
Amino Acids ◽  
Immune Cells ◽  
Nicotinamide Adenine Dinucleotide ◽  
Cell Activation ◽  
Immune Cell ◽  
Nerve Cells ◽  
Metabolic Reprogramming ◽  
Functional Plasticity ◽  
Immune Cell Activation ◽  
Oxide Synthase

Abstract Immune-cell activation and functional plasticity are closely linked to metabolic reprogramming that is required to supply the energy and substrates for such dynamic transformations. During such processes, immune cells metabolize many kinds of molecules including nucleic acids, sugars and lipids, which is called immunometabolism. This review will mainly focus on amino acids and their derivatives among such metabolites and describe the functions of these molecules in the immune system. Although amino acids are essential for, and well known as, substrates for protein synthesis, they are also metabolized as energy sources and as substrates for functional catabolites. For example, glutamine is metabolized to produce energy through glutaminolysis and tryptophan is consumed to supply nicotinamide adenine dinucleotide, whereas arginine is metabolized to produce nitric acid and polyamine by nitric oxide synthase and arginase, respectively. In addition, serine is catabolized to produce nucleotides and to induce methylation reactions. Furthermore, in addition to their intracellular functions, amino acids and their derivatives are secreted and have extracellular functions as immunotransmitters. Many amino acids and their derivatives have been classified as neurotransmitters and their functions are clear as transmitters between nerve cells, or between nerve cells and immune cells, functioning as immunotransmitters. Thus, this review will describe the intracellular and external functions of amino acid from the perspective of immunometabolism and immunotransmission.

scholarly journals Carbohydrate and Amino Acid Metabolism as Hallmarks for Innate Immune Cell Activation and Function

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 562 ◽  
Author(s):  
Haoxin Zhao ◽  
Lydia N. Raines ◽  
Stanley Ching-Cheng Huang
Keyword(s):  
Amino Acids ◽  
Immune Cells ◽  
Amino Acid Metabolism ◽  
Cell Activation ◽  
Acid Metabolism ◽  
Immune Cell ◽  
Innate Immune ◽  
Effector Functions ◽  
Immune Cell Activation ◽  
And Function

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.

scholarly journals Immunomodulation of Epithelium

1996 ◽  
Vol 10 (4) ◽  
pp. 243-248 ◽  
Author(s):  
Mary H Perdue
Keyword(s):  
Mast Cell ◽  
Immune Cells ◽  
Cell Activation ◽  
Immune Cell ◽  
Regulatory System ◽  
Mast Cell Activation ◽  
Immune Cell Activation ◽  
Inflammatory Conditions ◽  
Close Proximity ◽  
Antigenic Material

Many studies have provided evidence that the immune system is a key regulatory system of intestinal function. The interaction of immune cells with the gut epithelium plays an important role in host defence, acting to eliminate pathogens, antigens and other noxious material from the lumen of the gastrointestinal tract. During inflammatory conditions of the gut, the mucosa becomes packed with immune cells in close proximity to the enterocytes. Mediators released from these cells have profound effects on epithelial functions. The two main functions of the intestinal epithelium are to transport nutrients, ions and water, and to act as a barrier to prevent unimpeded uptake of antigenic material and microbes from the lumen. Both these functions are altered by immune reactions in response to various stimuli. Topics discussed include mast cells and epithelial function; mast cell-nerve interaction; mast cell activation; neutrophils, eosinophils and macrophages; T cells; and prostaglandins and immune cell activation.

Integrative immunophysiology in the intestinal mucosa

1994 ◽  
Vol 267 (2) ◽  
pp. G151-G165 ◽  
Author(s):  
M. H. Perdue ◽  
D. M. McKay
Keyword(s):  
Immune Cells ◽  
Cell Activation ◽  
Immune Cell ◽  
Intestinal Epithelial ◽  
Immune Cell Activation ◽  
Current State ◽  
Enteric Nerves ◽  
Host Defense Response ◽  
Acid Metabolites ◽  
Epithelial Physiology

Over the past ten years, it has become evident that intestinal epithelial functions such as ion secretion are a host defense response to the presence of antigens, microbes, and other noxious substances in the gut lumen. Such responses are mediated by the activation of immune cells in the mucosa causing release of chemical mediators that act directly or indirectly on the epithelium. Frequently, immune cell products stimulate enteric nerves resulting in amplification. Thus immune cells and nerves form interactive units that can recognize various stimuli both specifically and nonspecifically and initiate mechanisms to eliminate offending material. Here, we review the current state of knowledge regarding immune regulation of epithelial physiology with particular emphasis on the ability of immune cells and their products (biogenic amines, cytokines, arachidonic acid metabolites, oxidants) to alter electrolyte transport. The mast cell will be highlighted in this scheme as this cell has been, and continues to be, the focus of extensive research efforts. However, recently it has become apparent that cells such as lymphocytes, macrophages, and polymorphonuclear leukocytes also play important roles in immunophysiology. The effect of immune cell activation on epithelial functions other than transport, such as permeability, proliferation, and antigen presentation, will be described where appropriate. Finally, we will present evidence that the enterocyte can express an "activated" phenotype and thus participate directly in mucosal immune responses.

scholarly journals Diabetes Prevention by Immunomodulatory FTY720 Treatment in the LEW.1AR1-iddm Rat Despite Immune Cell Activation

Endocrinology ◽  
2010 ◽  
Vol 151 (8) ◽  
pp. 3555-3565 ◽  
Author(s):  
Anne Jörns ◽  
Klaus Jan Rath ◽  
Taivankhuu Terbish ◽  
Tanja Arndt ◽  
Andreas Meyer zu Vilsendorf ◽  
...  
Keyword(s):  
Lymph Nodes ◽  
Proinflammatory Cytokines ◽  
Immune Cells ◽  
Diabetes Prevention ◽  
Cell Activation ◽  
Immune Cell ◽  
Spontaneous Diabetes ◽  
Immune Cell Activation ◽  
Gene And Protein Expression ◽  
Draining Lymph Nodes

The prevention of diabetes by the immunomodulatory agent FTY720 (fingolimod) was studied in the LEW.1AR1-iddm (IDDM) rat, an animal model of human type 1 diabetes. Immune cell subtypes and cytokine profiles in pancreatic islets, secondary lymphoid tissue, and serum were analyzed for signs of immune cell activation. Animals were treated with FTY720 (1 mg/kg body weight) for 40 d starting on d 50 of life. Changes in gene and protein expression of cytokines, CD8 markers, monocyte chemoattractant protein-1, inducible NO synthase, and caspase 3 were evaluated. Treatment with FTY720 prevented diabetes manifestation and islet infiltration around d 60 of life, the usual time of spontaneous diabetes development. On d 120, 30 d after the end of FTY720 therapy, diabetes prevention persisted. However, six of 12 treated animals showed increased gene expression of IL-1β, TNF-α, and CD8 markers in pancreas-draining lymph nodes, indicating immune cell activation. In parallel, serum concentrations of these proinflammatory cytokines were increased. These six animals also showed macrophage infiltration without proinflammatory cytokine expression in a small minority (2–3%) of islets. Interestingly, regulatory T lymphocytes were significantly increased in the efferent vessels of the pancreas-draining lymph nodes only in animals without signs of immune cell activation but not in the rats with immune cell activation. This provides an indication for a lack of protective capacity in the animals with activated immune cells. Thus, FTY720 treatment prevented the manifestation of diabetes by promoting the retention of activated immune cells in the lymph nodes, thereby avoiding islet infiltration and β-cell destruction by proinflammatory cytokines.

scholarly journals Metabolic substrate utilization in stress-induced immune cells

2020 ◽  
Vol 8 (S1) ◽  
Author(s):  
Xiaomin Zhang ◽  
Fabian Zink ◽  
Felix Hezel ◽  
Josef Vogt ◽  
Ulrich Wachter ◽  
...  
Keyword(s):  
Immune Cells ◽  
Metabolic Pathways ◽  
Cell Activation ◽  
Immune Cell ◽  
Tca Cycle ◽  
Therapeutic Interventions ◽  
Functional Changes ◽  
Cell Functions ◽  
Immune Cell Activation ◽  
Metabolic Functions

AbstractImmune cell activation leads to the acquisition of new functions, such as proliferation, chemotaxis, and cytokine production. These functional changes require continuous metabolic adaption in order to sustain ATP homeostasis for sufficient host defense. The bioenergetic demands are usually met by the interconnected metabolic pathways glycolysis, TCA cycle, and oxidative phosphorylation. Apart from glucose, other sources, such as fatty acids and glutamine, are able to fuel the TCA cycle.Rising evidence has shown that cellular metabolism has a direct effect on the regulation of immune cell functions. Thus, quiescent immune cells maintain a basal metabolic state, which shifts to an accelerated metabolic level upon immune cell activation in order to promote key effector functions.This review article summarizes distinct metabolic signatures of key immune cell subsets from quiescence to activation and demonstrates a methodical concept of how to assess cellular metabolic pathways. It further discusses why metabolic functions are of rising interest for translational research and how they can be affected by the underlying pathophysiological condition and/or therapeutic interventions.

scholarly journals Exploiting immune cell metabolic machinery for functional HIV cure and the prevention of inflammaging

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 125 ◽  
Author(s):  
Clovis S. Palmer ◽  
Riya Palchaudhuri ◽  
Hassan Albargy ◽  
Mohamed Abdel-Mohsen ◽  
Suzanne M. Crowe
Keyword(s):  
Hiv Infection ◽  
Immune Cells ◽  
Cell Activation ◽  
Viral Infections ◽  
Immune Cell ◽  
Metabolic Reprogramming ◽  
Low Grade ◽  
Hiv Cure ◽  
Cell Functions ◽  
Age Related

An emerging paradigm in immunology suggests that metabolic reprogramming and immune cell activation and functions are intricately linked. Viral infections, such as HIV infection, as well as cancer force immune cells to undergo major metabolic challenges. Cells must divert energy resources in order to mount an effective immune response. However, the fact that immune cells adopt specific metabolic programs to provide host defense against intracellular pathogens and how this metabolic shift impacts immune cell functions and the natural course of diseases have only recently been appreciated. A clearer insight into how these processes are inter-related will affect our understanding of several fundamental aspects of HIV persistence. Even in patients with long-term use of anti-retroviral therapies, HIV infection persists and continues to cause chronic immune activation and inflammation, ongoing and cumulative damage to multiple organs systems, and a reduction in life expectancy. HIV-associated fundamental changes to the metabolic machinery of the immune system can promote a state of “inflammaging”, a chronic, low-grade inflammation with specific immune changes that characterize aging, and can also contribute to the persistence of HIV in its reservoirs. In this commentary, we will bring into focus evolving concepts on how HIV modulates the metabolic machinery of immune cells in order to persist in reservoirs and how metabolic reprogramming facilitates a chronic state of inflammation that underlies the development of age-related comorbidities. We will discuss how immunometabolism is facilitating the changing paradigms in HIV cure research and outline the novel therapeutic opportunities for preventing inflammaging and premature development of age-related conditions in HIV+individuals.

scholarly journals Regulation of Immune Cell Functions by Metabolic Reprogramming

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Jaehong Kim
Keyword(s):  
T Cells ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Immune Cell ◽  
Aerobic Glycolysis ◽  
Metabolic Changes ◽  
Metabolic Reprogramming ◽  
Functional Plasticity ◽  
Inflammatory Reactions ◽  
Cell Functions

Recent findings show that the metabolic status of immune cells can determine immune responses. Metabolic reprogramming between aerobic glycolysis and oxidative phosphorylation, previously speculated as exclusively observable in cancer cells, exists in various types of immune and stromal cells in many different pathological conditions other than cancer. The microenvironments of cancer, obese adipose, and wound-repairing tissues share common features of inflammatory reactions. In addition, the metabolic changes in macrophages and T cells are now regarded as crucial for the functional plasticity of the immune cells and responsible for the progression and regression of many pathological processes, notably cancer. It is possible that metabolic changes in the microenvironment induced by other cellular components are responsible for the functional plasticity of immune cells. This review explores the molecular mechanisms responsible for metabolic reprogramming in macrophages and T cells and also provides a summary of recent updates with regard to the functional modulation of the immune cells by metabolic changes in the microenvironment, notably the tumor microenvironment.

scholarly journals Deoxyribonuclease 1-Mediated Clearance of Circulating Chromatin Prevents From Immune Cell Activation and Pro-inflammatory Cytokine Production, a Phenomenon Amplified by Low Trap1 Activity: Consequences for Systemic Lupus Erythematosus

2021 ◽  
Vol 12 ◽  
Author(s):  
Jasmin Felux ◽  
Annika Erbacher ◽  
Magali Breckler ◽  
Roxane Hervé ◽  
Delphine Lemeiter ◽  
...  
Keyword(s):  
Immune Cells ◽  
Lupus Erythematosus ◽  
Cell Activation ◽  
Immune Cell ◽  
Wild Type ◽  
Systemic Lupus ◽  
Immune Cell Activation ◽  
Deficient Mice

Increased concentrations of circulating chromatin, especially oligo-nucleosomes, are observed in sepsis, cancer and some inflammatory autoimmune diseases like systemic lupus erythematosus (SLE). In SLE, circulating nucleosomes mainly result from increased apoptosis and decreased clearance of apoptotic cells. Once released, nucleosomes behave both as an autoantigen and as a damage-associated molecular pattern (DAMP) by activating several immune cells, especially pro-inflammatory cells. Deoxyribonuclease 1 (DNase1) is a major serum nuclease whose activity is decreased in mouse and human lupus. Likewise, the mitochondrial chaperone tumor necrosis factor (TNF) receptor-associated protein-1 (Trap1) protects against oxidative stress, which is increased in SLE. Here, using wild type, DNase1-deficient and DNase1/Trap1-deficient mice, we demonstrate that DNase1 is a major serum nuclease involved in chromatin degradation, especially when the plasminogen system is activated. In vitro degradation assays show that chromatin digestion is strongly impaired in serum from DNase1/Trap1-deficient mice as compared to wild type mice. In vivo, after injection of purified chromatin, clearance of circulating chromatin is delayed in DNase1/Trap1-deficient mice in comparison to wild type mice. Since defective chromatin clearance may lead to chromatin deposition in tissues and subsequent immune cell activation, spleen cells were stimulated in vitro with chromatin. Splenocytes were activated by chromatin, as shown by interleukin (IL)-12 secretion and CD69 up-regulation. Moreover, cell activation was exacerbated when Trap1 is deficient. Importantly, we also show that cytokines involved in lupus pathogenesis down-regulate Trap1 expression in splenocytes. Therefore, combined low activities of both DNase1 and Trap1 lead to an impaired degradation of chromatin in vitro, delayed chromatin clearance in vivo and enhanced activation of immune cells. This situation may be encountered especially, but not exclusively, in SLE by the negative action of cytokines on Trap1 expression.

Neuroinflammation and Neurodegenerative Diseases

2016 ◽  
Author(s):  
Taylor R. Jay ◽  
Shane M. Bemiller ◽  
Lee E. Neilson ◽  
Paul J. Cheng-Hathaway ◽  
Bruce T. Lamb
Keyword(s):  
Neurodegenerative Diseases ◽  
Immune Cells ◽  
Cell Activation ◽  
Immune Cell ◽  
Active Role ◽  
Immune Cell Activation ◽  
Excitotoxic Damage ◽  
And Function ◽  
Inflammatory Molecules ◽  
The Brain

Neuroinflammation has long been associated with many neurodegenerative diseases (NDDs). Immune-related genetic and environmental risk factors have recently been identified for NDDs, suggesting that neuroinflammation can play an active role in modifying NDD pathologies. Immune cells that underlie this neuroinflammatory response can have both beneficial and detrimental roles in NDDs. These cells can engage in clearance of debris and provide important survival factors to neighboring neurons. However, these cells can also release inflammatory molecules that promote oxidative stress and excitotoxic damage in surrounding neurons, and aberrantly clear healthy cells and structures from the brain. In turn, the cells within the brain play important roles in determining the phenotype and function of these immune cells, and changes in the interaction among these cells in the context of disease can lead to detrimental immune cell activation. There has been recent interest in developing inflammation-related biomarkers to help diagnose NDDs and immune-targeted therapeutics.

scholarly journals Immunometabolism: Towards a Better Understanding the Mechanism of Parasitic Infection and Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Jing-yue Chen ◽  
Ji-kai Zhou ◽  
Wei Pan
Keyword(s):  
Cell Activation ◽  
Regulatory Mechanism ◽  
Immune Cell ◽  
Parasitic Infection ◽  
Underlying Mechanism ◽  
Intervention Strategies ◽  
Metabolic Reprogramming ◽  
Research Progress ◽  
Immune Cell Activation

As a relatively successful pathogen, several parasites can establish long-term infection in host. This “harmonious symbiosis” status relies on the “precise” manipulation of host immunity and metabolism, however, the underlying mechanism is still largely elusive. Immunometabolism is an emerging crossed subject in recent years. It mainly discusses the regulatory mechanism of metabolic changes on reprogramming the key transcriptional and post-transcriptional events related to immune cell activation and effect, which provides a novel insight for understanding how parasites regulate the infection and immunity in hosts. The present study reviewed the current research progress on metabolic reprogramming mechanism exploited by parasites to modulate the function in various immune cells, highlighting the future exploitation of key metabolites or metabolic events to clarify the underlying mechanism of anti-parasite immunity and design novel intervention strategies against parasitic infection.

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