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Immune glycolysis

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https://www.readbyqxmd.com/read/28426686/reactive-oxygen-species-are-required-for-driving-efficient-and-sustained-aerobic-glycolysis-during-cd4-t-cell-activation
#1
Dana M Previte, Erin C O'Connor, Elizabeth A Novak, Christina P Martins, Kevin P Mollen, Jon D Piganelli
The immune system is necessary for protecting against various pathogens. However, under certain circumstances, self-reactive immune cells can drive autoimmunity, like that exhibited in type 1 diabetes (T1D). CD4+ T cells are major contributors to the immunopathology in T1D, and in order to drive optimal T cell activation, third signal reactive oxygen species (ROS) must be present. However, the role ROS play in mediating this process remains to be further understood. Recently, cellular metabolic programs have been shown to dictate the function and fate of immune cells, including CD4+ T cells...
2017: PloS One
https://www.readbyqxmd.com/read/28420478/-research-progress-on-metabolism-of-monocytes-and-macrophages-in-sepsis
#2
Changli Wang, Lulong Bo, Xiaoming Deng
During sepsis, circulating leukocytes are in a hyper inflammatory state, and with the progress of the inflammation, immune cells may become tolerated. Glycolysis and pentose phosphate pathway are up-regulated but oxidative phosphorylation is suppressed in hyper inflammatory cells, whereas during immune tolerance, glycolysis is often down-regulated. In this review, we will summarize the changes of cellular metabolic pathways in monocytes and macrophages during sepsis. We also review how the metabolism of glucose, amino acids, and fatty acids affect the function of monocytes and macrophages in sepsis...
April 2017: Zhonghua Wei Zhong Bing Ji Jiu Yi Xue
https://www.readbyqxmd.com/read/28416194/foxp3-reprograms-t-cell-metabolism-to-function-in-low-glucose-high-lactate-environments
#3
Alessia Angelin, Luis Gil-de-Gómez, Satinder Dahiya, Jing Jiao, Lili Guo, Matthew H Levine, Zhonglin Wang, William J Quinn, Piotr K Kopinski, Liqing Wang, Tatiana Akimova, Yujie Liu, Tricia R Bhatti, Rongxiang Han, Benjamin L Laskin, Joseph A Baur, Ian A Blair, Douglas C Wallace, Wayne W Hancock, Ulf H Beier
Immune cells function in diverse metabolic environments. Tissues with low glucose and high lactate concentrations, such as the intestinal tract or ischemic tissues, frequently require immune responses to be more pro-tolerant, avoiding unwanted reactions against self-antigens or commensal bacteria. T-regulatory cells (Tregs) maintain peripheral tolerance, but how Tregs function in low-glucose, lactate-rich environments is unknown. We report that the Treg transcription factor Foxp3 reprograms T cell metabolism by suppressing Myc and glycolysis, enhancing oxidative phosphorylation, and increasing nicotinamide adenine dinucleotide oxidation...
April 11, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28407895/test-for-l-glutamate-inhibition-of-growth-of-alternaria-alternata-by-inducing-resistance-in-tomato-fruit
#4
Jiali Yang, Cui Sun, Da Fu, Ting Yu
Although numerous studies have reported the involvement of glutamate in plant abiotic stress, relatively little is known about the role of glutamate in plant defence against pathogens. To gain further knowledge, we investigated the effect of glutamate on Alternaria alternata in tomato fruit. A multidisciplinary approach was pursued, combining exogenous glutamate applications, enzymatic activity measurements and real-time quantitative PCR analysis. The results showed glutamate significantly reduced the disease incidence in tomato caused by A...
September 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28400131/linking-tumor-glycolysis-and-immune-evasion-in-cancer-emerging-concepts-and-therapeutic-opportunities
#5
REVIEW
Shanmugasundaram Ganapathy-Kanniappan
Metabolic reprogramming and immune evasion are two hallmarks of cancer. Metabolic reprogramming is exemplified by cancer's propensity to utilize glucose at an exponential rate which in turn is linked with "aerobic glycolysis", popularly known as the "Warburg effect". Tumor glycolysis is pivotal for the efficient management of bioenergetics and uninterrupted cancer growth. Mounting evidence suggests that tumor glycolysis also plays a key role in instigating immunosuppressive networks that are critical for cancer cells to escape immune surveillance ("immune evasion")...
April 8, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28389590/cutting-edge-increased-autoimmunity-risk-in-glycogen-storage-disease-type-1b-is-associated-with-a-reduced-engagement-of-glycolysis-in-t-cells-and-an-impaired-regulatory-t-cell-function
#6
Daniela Melis, Fortunata Carbone, Giorgia Minopoli, Claudia La Rocca, Francesco Perna, Veronica De Rosa, Mario Galgani, Generoso Andria, Giancarlo Parenti, Giuseppe Matarese
Glycogen storage disease type 1b (GSD-1b) is an autosomal-recessive disease caused by mutation of glucose-6-phosphate transporter and characterized by altered glycogen/glucose homeostasis. A higher frequency of autoimmune diseases has been observed in GSD-1b patients, but the molecular determinants leading to this phenomenon remain unknown. To address this question, we investigated the effect of glucose-6-phosphate transporter mutation on immune cell homeostasis and CD4(+) T cell functions. In GSD-1b subjects, we found lymphopenia and a reduced capacity of T cells to engage glycolysis upon TCR stimulation...
April 7, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28386604/hypoxia-determines-survival-outcomes-of-bacterial-infection-through-hif-1alpha-dependent-re-programming-of-leukocyte-metabolism
#7
A A R Thompson, R S Dickinson, F Murphy, J P Thomson, H M Marriott, A Tavares, J Willson, L Williams, A Lewis, A Mirchandani, P Dos Santos Coelho, C Doherty, E Ryan, E Watts, N M Morton, S Forbes, R H Stimson, A G Hameed, N Arnold, J A Preston, A Lawrie, V Finisguerra, M Mazzone, P Sadiku, J Goveia, F Taverna, P Carmeliet, S J Foster, E R Chilvers, A S Cowburn, D H Dockrell, R S Johnson, R R Meehan, M K B Whyte, S R Walmsley
Hypoxia and bacterial infection frequently co-exist, in both acute and chronic clinical settings, and typically result in adverse clinical outcomes. To ameliorate this morbidity, we investigated the interaction between hypoxia and the host response. In the context of acute hypoxia, both S. aureus and S. pneumoniae infections rapidly induced progressive neutrophil mediated morbidity and mortality, with associated hypothermia and cardiovascular compromise. Preconditioning animals through longer exposures to hypoxia, prior to infection, prevented these pathophysiological responses and profoundly dampened the transcriptome of circulating leukocytes...
February 10, 2017: Science Immunology
https://www.readbyqxmd.com/read/28368517/enhanced-glycolytic-metabolism-contributes-to-cardiac-dysfunction-in-polymicrobial-sepsis
#8
Zhibo Zheng, He Ma, Xia Zhang, Fei Tu, Xiaohui Wang, Tuanzhu Ha, Min Fan, Li Liu, Jingjing Xu, Kaiking Yu, Ruitao Wang, John Kalbfleisch, Race Kao, David Williams, Chuanfu Li
Background: Cardiac dysfunction is present in >40% of sepsis patients and is associated with mortality rates of up to 70%. Recent evidence suggests that glycolytic metabolism plays a critical role in host defense and inflammation. Activation of Toll-like receptors on immune cells can enhance glycolytic metabolism. This study investigated whether modulation of glycolysis by inhibition of hexokinase will be beneficial to septic cardiomyopathy. Methods: Male C57B6/J mice were treated with a hexokinase inhibitor (2-deoxy-D-glucose, 2-DG, 0...
March 22, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/28363691/myc-and-hif-in-shaping-immune-response-and-immune-metabolism
#9
REVIEW
J N Rashida Gnanaprakasam, John William Sherman, Ruoning Wang
Upon antigen stimulation, quiescent naive T cells undergo a phase of cell mass accumulation followed by cell cycle entry, clonal expansion, differentiation into functional subsets and back again to a quiescent state as they develop into memory cells. The transitions between these distinct cellular states place unique metabolic demands on energy, redox and biosynthesis. To fulfill these demands, T cells switch back and forth between their primary catabolic pathways. While quiescent naive and memory T cells largely rely on the oxidation of fatty acids and glucose, active T cells rely on glycolysis and glutaminolysis to sustain cell growth, proliferation and differentiation...
March 23, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/28360422/immunometabolism-in-early-and-late-stages-of-rheumatoid-arthritis
#10
REVIEW
Cornelia M Weyand, Jörg J Goronzy
One of the fundamental traits of immune cells in rheumatoid arthritis (RA) is their ability to proliferate, a property shared with the joint-resident cells that form the synovial pannus. The building of biomass imposes high demands for energy and biosynthetic precursors, implicating metabolic control as a basic disease mechanism. During preclinical RA, when autoreactive T cells expand and immunological tolerance is broken, the main sites of disease are the secondary lymphoid tissues. Naive CD4(+) T cells from patients with RA have a distinct metabolic signature, characterized by dampened glycolysis, low ATP levels and enhanced shunting of glucose into the pentose phosphate pathway...
March 31, 2017: Nature Reviews. Rheumatology
https://www.readbyqxmd.com/read/28348977/taming-tumor-glycolysis-and-potential-implications-for-immunotherapy
#11
REVIEW
Shanmugasundaram Ganapathy-Kanniappan
Immune evasion and deregulation of energy metabolism play a pivotal role in cancer progression. Besides the coincidence in their historical documentation and concurrent recognition as hallmarks of cancer, both immune evasion and metabolic deregulation may be functionally linked as well. For example, the metabolic phenotype, particularly tumor glycolysis (aerobic glycolysis), impacts the tumor microenvironment (TME), which in turn acts as a major barrier for successful targeting of cancer by antitumor immune cells and other therapeutics...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28345074/single-cell-rna-seq-and-computational-analysis-using-temporal-mixture-modelling-resolves-th1-tfh-fate-bifurcation-in-malaria
#12
Tapio Lönnberg, Valentine Svensson, Kylie R James, Daniel Fernandez-Ruiz, Ismail Sebina, Ruddy Montandon, Megan S F Soon, Lily G Fogg, Arya Sheela Nair, Urijah Liligeto, Michael J T Stubbington, Lam-Ha Ly, Frederik Otzen Bagger, Max Zwiessele, Neil D Lawrence, Fernando Souza-Fonseca-Guimaraes, Patrick T Bunn, Christian R Engwerda, William R Heath, Oliver Billker, Oliver Stegle, Ashraful Haque, Sarah A Teichmann
Differentiation of naïve CD4(+) T cells into functionally distinct T helper subsets is crucial for the orchestration of immune responses. Due to extensive heterogeneity and multiple overlapping transcriptional programs in differentiating T cell populations, this process has remained a challenge for systematic dissection in vivo. By using single-cell transcriptomics and computational analysis using a temporal mixtures of Gaussian processes model, termed GPfates, we reconstructed the developmental trajectories of Th1 and Tfh cells during blood-stage Plasmodium infection in mice...
March 3, 2017: Science Immunology
https://www.readbyqxmd.com/read/28318896/role-of-ahr-and-hif-1%C3%AE-in-glioblastoma-metabolism
#13
REVIEW
Galina Gabriely, Michael A Wheeler, Maisa C Takenaka, Francisco J Quintana
Glioblastoma (GBM) progression is associated with metabolic remodeling in both glioma and immune cells, resulting in the use of aerobic glycolysis as the main source of energy and biosynthetic molecules. The transcription factor hypoxia-inducible factor (HIF)-1α drives this metabolic reorganization. Oxygen levels, as well as other factors, control the activity of HIF-1α. In addition, the ligand-activated transcription factor aryl hydrocarbon receptor (AHR) modulates tumor-specific immunity and can also participate in metabolic remodeling...
March 16, 2017: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/28293240/extracellular-acidification-inhibits-the-ros-dependent-formation-of-neutrophil-extracellular-traps
#14
Martina Behnen, Sonja Möller, Antonia Brozek, Matthias Klinger, Tamás Laskay
The inflammatory microenvironment is commonly characterized by extracellular acidosis (pH < 7.35). Sensitivity to pH, CO2 or bicarbonate concentrations allows neutrophils to react to changes in their environment and to detect inflamed areas in the tissue. One important antimicrobial effector mechanism is the production of neutrophil extracellular traps (NETs), which are released during a programmed reactive oxygen species (ROS)-dependent cell death, the so-called NETosis. Although several functions of neutrophils have been analyzed under acidic conditions, the effect of extracellular acidosis on NETosis remains mainly unexplored and the available experimental results are contradictory...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28290453/suppressive-il-17a-foxp3-and-ex-th17-il-17a-neg-foxp3-treg-cells-are-a-source-of-tumour-associated-treg-cells
#15
Stephanie Downs-Canner, Sara Berkey, Greg M Delgoffe, Robert P Edwards, Tyler Curiel, Kunle Odunsi, David L Bartlett, Nataša Obermajer
Th17 and regulatory T (Treg) cells are integral in maintaining immune homeostasis and Th17-Treg imbalance is associated with inflammatory immunosuppression in cancer. Here we show that Th17 cells are a source of tumour-induced Foxp3(+) cells. In addition to natural (n)Treg and induced (i)Treg cells that develop from naive precursors, suppressive IL-17A(+)Foxp3(+) and ex-Th17 Foxp3(+) cells are converted from IL-17A(+)Foxp3(neg) cells in tumour-bearing mice. Metabolic phenotyping of Foxp3-expressing IL-17A(+), ex-Th17 and iTreg cells demonstrates the dissociation between the metabolic fitness and the suppressive function of Foxp3-expressing Treg cell subsets...
March 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28287112/glucocorticoid-receptor-promotes-the-function-of-myeloid-derived-suppressor-cells-by-suppressing-hif1%C3%AE-dependent-glycolysis
#16
Yun Lu, Huanrong Liu, Yujing Bi, Hui Yang, Yan Li, Jian Wang, Zhengguo Zhang, Yu Wang, Chunxiao Li, Anna Jia, Linian Han, Ying Hu, Yong Zhao, Ruoning Wang, Guangwei Liu
Immunomodulatory signaling imposes tight regulations on metabolic programs within immune cells and consequentially determines immune response outcomes. Although the glucocorticoid receptor (GR) has been recently implicated in regulating the function of myeloid-derived suppressor cells (MDSCs), whether the dysregulation of GR in MDSCs is involved in immune-mediated hepatic diseases and how GR regulates the function of MDSCs in such a context remains unknown. Here, we revealed the dysregulation of GR expression in MDSCs during innate immunological hepatic injury (IMH) and found that GR regulates the function of MDSCs through modulating HIF1α-dependent glycolysis...
March 13, 2017: Cellular & Molecular Immunology
https://www.readbyqxmd.com/read/28275139/the-cytokine-response-to-lipopolysaccharide-does-not-predict-the-host-response-to-infection
#17
Benjamin A Fensterheim, Yin Guo, Edward R Sherwood, Julia K Bohannon
The magnitude of the LPS-elicited cytokine response is commonly used to assess immune function in critically ill patients. A suppressed response, known as endotoxin tolerance, is associated with worse outcomes, yet endotoxin tolerance-inducing TLR4 ligands are known to protect animals from infection. Thus, it remains unknown whether the magnitude of the LPS-elicited cytokine response provides an accurate assessment of antimicrobial immunity. To address this, the ability of diverse TLR ligands to modify the LPS-elicited cytokine response and resistance to infection were assessed...
April 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28270822/biochar-amendment-modifies-expression-of-soybean-and-rhizoctonia-solani-genes-leading-to-increased-severity-of-rhizoctonia-foliar-blight
#18
Tanya Copley, Stéphane Bayen, Suha Jabaji
Application of biochar, a pyrolyzed biomass from organic sources, to agricultural soils is considered a promising strategy to sustain soil fertility leading to increased plant productivity. It is also known that applications of biochar to soilless potting substrates and to soil increases resistance of plants against diseases, but also bear the potential to have inconsistent and contradictory results depending on the type of biochar feedstock and application rate. The following study examined the effect of biochar produced from maple bark on soybean resistance against Rhizoctonia foliar blight (RFB) disease caused by Rhizoctonia solani, and examined the underlying molecular responses of both soybean and R...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28249898/defining-cancer-subpopulations-by-adaptive-strategies-rather-than-molecular-properties-provides-novel-insights-into-intratumoral-evolution
#19
Arig Ibrahim-Hashim, Mark Robertson-Tessi, Pedro Enrizues-Navas, Mehdi Damaghi, Yoganand Balagurunathan, Jonathan W Wojtkowiak, Shonagh Russell, Kam Yoonseok, Mark C Lloyd, Marilyn M Bui, Joel S Brown, Alexander Ra Anderson, Robert J Gillies, Robert A Gatenby
Ongoing intratumoral evolution is apparent in molecular variations among cancer cells from different regions of the same tumor, but genetic data alone provide little insight into environmental selection forces and cellular phenotypic adaptations that govern the underlying Darwinian dynamics. In three spontaneous murine cancers (prostate cancers in TRAMP and PTEN mice, pancreatic cancer in KPC mice), we identified two subpopulations with distinct niche-construction adaptive strategies that remained stable in culture: (1) Invasive cells that produce an acidic environment via upregulated aerobic glycolysis, and (2) Non-invasive cells that were angiogenic and metabolically near-normal...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28225071/resolution-of-tlr2-induced-inflammation-through-manipulation-of-metabolic-pathways-in-rheumatoid-arthritis
#20
Trudy McGarry, Monika Biniecka, Wei Gao, Deborah Cluxton, Mary Canavan, Siobhan Wade, Sarah Wade, Lorna Gallagher, Carl Orr, Douglas J Veale, Ursula Fearon
During inflammation, immune cells activated by toll-like receptors (TLRs) have the ability to undergo a bioenergetic switch towards glycolysis in a manner similar to that observed in tumour cells. While TLRs have been implicated in the pathogenesis of rheumatoid arthritis (RA), their role in regulating cellular metabolism in synovial cells, however, is still unknown. In this study, we investigated the effect of TLR2-activation on mitochondrial function and bioenergetics in primary RA-synovial fibroblast cells (RASFC), and further determined the role of glycolytic blockade on TLR2-induced inflammation in RASFC using glycolytic inhibitor 3-(3-pyridinyl)-1-(4-pyridinyl)-2-propen-1-one (3PO)...
February 22, 2017: Scientific Reports
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