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Immune glycolysis

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https://www.readbyqxmd.com/read/27918097/sugars-and-fat-a-healthy-way-to-generate-functional-regulatory-t-cells
#1
Sarah Sharon Gabriel, Axel Kallies
Cellular metabolism has emerged as an important regulator of adaptive immunity. While the metabolic requirements of conventional T cells are increasingly understood, the role of cellular metabolism in Foxp3(+) regulatory T (Treg) cells is less clear. Although it is well accepted that repression of Akt/mTOR, HIF-1α and aerobic glycolysis are important for the efficient generation of Treg cells in vitro, clear evidence how these pathways impact on Treg-cell development in vivo is limited. Furthermore, newer studies have shown that the same pathways that appear to suppress Treg-cell development are active in and required for functionally mature Treg cells...
December 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27911401/an-optimized-protocol-to-analyze-glycolysis-and-mitochondrial-respiration-in-lymphocytes
#2
Javier Traba, Pietro Miozzo, Billur Akkaya, Susan K Pierce, Munir Akkaya
Lymphocytes respond to a variety of stimuli by activating intracellular signaling pathways, which in turn leads to rapid cellular proliferation, migration and differentiation, and cytokine production. All of these events are tightly linked to the energy status of the cell, and therefore studying the energy-producing pathways may give clues about the overall functionality of these cells. The extracellular flux analyzer is a commonly used device for evaluating the performance of glycolysis and mitochondrial respiration in many cell types...
November 21, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/27910764/metabolic-regulation-of-natural-killer-cell-ifn-%C3%AE-production
#3
Annelise Y Mah, Megan A Cooper
Metabolism is critical for a host of cellular functions and provides a source of intracellular energy. It has been recognized recently that metabolism also regulates differentiation and effector functions of immune cells. Although initial work in this field has focused largely on T lymphocytes, recent studies have demonstrated metabolic control of innate immune cells, including natural killer (NK) cells. Here, we review what is known regarding the metabolic requirements for NK cell activation, focusing on NK cell production of interferon-gamma (IFN-γ)...
2016: Critical Reviews in Immunology
https://www.readbyqxmd.com/read/27904969/metabolic-responses-and-omics-technologies-for-elucidating-the-effects-of-heat-stress-in-dairy-cows
#4
REVIEW
Li Min, Shengguo Zhao, He Tian, Xu Zhou, Yangdong Zhang, Songli Li, Hongjian Yang, Nan Zheng, Jiaqi Wang
Heat stress (HS) negatively affects various industries that rely on animal husbandry, particularly the dairy industry. A better understanding of metabolic responses in HS dairy cows is necessary to elucidate the physiological mechanisms of HS and offer a new perspective for future research. In this paper, we review the current knowledge of responses of body metabolism (lipid, carbohydrate, and protein), endocrine profiles, and bovine mammary epithelial cells during HS. Furthermore, we summarize the metabolomics and proteomics data that have revealed the metabolite profiles and differentially expressed proteins that are a feature of HS in dairy cows...
November 30, 2016: International Journal of Biometeorology
https://www.readbyqxmd.com/read/27903739/homocysteine-activates-b-cells-via-regulating-pkm2-dependent-metabolic-reprogramming
#5
Jiacheng Deng, Silin Lü, Huiying Liu, Bo Liu, Changtao Jiang, Qingbo Xu, Juan Feng, Xian Wang
The overactivation of immune cells plays an important role in the pathogenesis of hyperhomocysteinemia (HHcy)-accelerated atherosclerosis. Homocysteine (Hcy) activates B cell proliferation and Ab secretion; however, the underlying mechanisms for these effects remain largely unknown. Metabolic reprogramming is critical for lymphocyte activation and effector function. In this study, we showed that Hcy-activated B cells displayed an increase in both oxidative phosphorylation and glycolysis, with a tendency to shift toward the latter, as well as an accumulation of intermediates in the pentose phosphate pathway, to provide energy and biosynthetic substrates for cell growth and function...
November 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27898346/amp-kinase-promotes-bcl6-expression-in-both-mouse-and-human-t-cells
#6
Markus M Xie, Tohti Amet, Hong Liu, Qigui Yu, Alexander L Dent
The transcription factor Bcl6 is a master regulator of follicular helper T (TFH) cells, and understanding the signaling pathway that induces Bcl6 and TFH cell differentiation is therefore critical. IL-2 produced during T cell activation inhibits Bcl6 expression but how TFH cells evade IL-2 inhibition is not completely understood. Here we show that Bcl6 is highly up-regulated in activated CD4 T cells following glucose deprivation (GD), and this pathway is insensitive to inhibition by IL-2. Similar to GD, the glucose analog 2-deoxyglucose (2DG) inhibits glycolysis, and 2DG induced Bcl6 expression in activated CD4 T cells...
November 26, 2016: Molecular Immunology
https://www.readbyqxmd.com/read/27884183/rna-sequencing-for-profiling-goat-milk-transcriptome-in-colostrum-and-mature-milk
#7
Alessandra Crisà, Fabrizio Ferrè, Giovanni Chillemi, Bianca Moioli
BACKGROUND: In this work we aimed at sequencing and assembling the goat milk transcriptome corresponding at colostrum and 120 days of lactation. To reconstruct transcripts we used both the genome as reference, and a de novo assembly approach. Additionally, we aimed at identifying the differentially expressed genes (DEGs) between the two lactation stages and at analyzing the expression of genes involved in oligosaccharides metabolism. RESULTS: A total of 44,635 different transcripts, organized in 33,757 tentative genes, were obtained using the goat genome as reference...
November 25, 2016: BMC Veterinary Research
https://www.readbyqxmd.com/read/27883186/lactate-at-the-crossroads-of-metabolism-inflammation-and-autoimmunity
#8
Valentina Pucino, Michele Bombardieri, Costantino Pitzalis, Claudio Mauro
For a long time after its discovery at the beginning of the 20th century, lactate was considered a waste product of cellular metabolism. Starting in the early '90s, however, lactate has begun to be recognised as an active molecule capable of modulating the immune response. Inflammatory sites, including in rheumatoid arthritis synovitis, are characterised by the accumulation of lactate, which is partly responsible for the establishment of an acidic environment. We have recently reported that T cells sense lactate via the expression of specific transporters, leading to inhibition of their motility...
November 24, 2016: European Journal of Immunology
https://www.readbyqxmd.com/read/27883071/mint3-apba3-depletion-ameliorates-severe-murine-influenza-pneumonia-and-macrophage-cytokine-production-in-response-to-the-influenza-virus
#9
Takayuki Uematsu, Tomoko Fujita, Hiroki J Nakaoka, Toshiro Hara, Noritada Kobayashi, Yoshinori Murakami, Motoharu Seiki, Takeharu Sakamoto
Influenza virus (IFV) infection is a common cause of severe pneumonia. Studies have suggested that excessive activation of the host immune system including macrophages is responsible for the severe pathologies mediated by IFV infection. Here, we focused on the X11 protein family member Mint3/Apba3, known to promote ATP production via glycolysis by activating hypoxia inducible factor-1 (HIF-1) in macrophages, and examined its roles in lung pathogenesis and anti-viral defence upon IFV infection. Mint3-deficient mice exhibited improved influenza pneumonia with reduced inflammatory cytokines/chemokine levels and neutrophil infiltration in the IFV-infected lungs without alteration in viral burden, type-I interferon production, or acquired immunity...
November 24, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27866838/glutaminolysis-and-fumarate-accumulation-integrate-immunometabolic-and-epigenetic-programs-in-trained-immunity
#10
Rob J W Arts, Boris Novakovic, Rob Ter Horst, Agostinho Carvalho, Siroon Bekkering, Ekta Lachmandas, Fernando Rodrigues, Ricardo Silvestre, Shih-Chin Cheng, Shuang-Yin Wang, Ehsan Habibi, Luís G Gonçalves, Inês Mesquita, Cristina Cunha, Arjan van Laarhoven, Frank L van de Veerdonk, David L Williams, Jos W M van der Meer, Colin Logie, Luke A O'Neill, Charles A Dinarello, Niels P Riksen, Reinout van Crevel, Clary Clish, Richard A Notebaart, Leo A B Joosten, Hendrik G Stunnenberg, Ramnik J Xavier, Mihai G Netea
Induction of trained immunity (innate immune memory) is mediated by activation of immune and metabolic pathways that result in epigenetic rewiring of cellular functional programs. Through network-level integration of transcriptomics and metabolomics data, we identify glycolysis, glutaminolysis, and the cholesterol synthesis pathway as indispensable for the induction of trained immunity by β-glucan in monocytes. Accumulation of fumarate, due to glutamine replenishment of the TCA cycle, integrates immune and metabolic circuits to induce monocyte epigenetic reprogramming by inhibiting KDM5 histone demethylases...
November 16, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/27856732/trypanosoma-brucei-metabolite-indolepyruvate-decreases-hif-1%C3%AE-and-glycolysis-in-macrophages-as-a-mechanism-of-innate-immune-evasion
#11
Anne F McGettrick, Sarah E Corcoran, Paul J G Barry, Jennifer McFarland, Cécile Crès, Anne M Curtis, Edward Franklin, Sinéad C Corr, K Hun Mok, Eoin P Cummins, Cormac T Taylor, Luke A J O'Neill, Derek P Nolan
The parasite Trypanasoma brucei causes African trypanosomiasis, known as sleeping sickness in humans and nagana in domestic animals. These diseases are a major burden in the 36 sub-Saharan African countries where the tsetse fly vector is endemic. Untreated trypanosomiasis is fatal and the current treatments are stage-dependent and can be problematic during the meningoencephalitic stage, where no new therapies have been developed in recent years and the current drugs have a low therapeutic index. There is a need for more effective treatments and a better understanding of how these parasites evade the host immune response will help in this regard...
November 29, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27852741/sensitivity-to-restimulation-induced-cell-death-is-linked-to-glycolytic-metabolism-in-human-t-cells
#12
Sasha E Larsen, Abegail Bilenkin, Tatiana N Tarasenko, Swadhinya Arjunaraja, Jeffrey R Stinson, Peter J McGuire, Andrew L Snow
Restimulation-induced cell death (RICD) regulates immune responses by restraining effector T cell expansion and limiting nonspecific damage to the host. RICD is triggered by re-engagement of the TCR on a cycling effector T cell, resulting in apoptosis. It remains unclear how RICD sensitivity is calibrated in T cells derived from different individuals or subsets. In this study we show that aerobic glycolysis strongly correlates with RICD sensitivity in human CD8(+) effector T cells. Reducing glycolytic activity or glucose availability rendered effector T cells significantly less sensitive to RICD...
November 16, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/27832958/hypoxia-inducible-factor-prolyl-4-hydroxylase-inhibition-in-cardiometabolic-diseases
#13
REVIEW
Peppi Koivunen, Raisa Serpi, Elitsa Y Dimova
Hypoxia-inducible factor prolyl 4-hydroxylases (HIF-P4Hs, also called PHDs and EglNs) are enzymes that act as cellular oxygen sensors. They are the main downregulators of the hypoxia-inducible factor (HIF). HIF-P4Hs can be targeted with small molecule inhibitors, which stabilize HIF under normoxia and initiate the hypoxia response. Such inhibitors are in phase 2 and 3 clinical trials for the treatment of anemia due to their ability to induce erythropoietin and iron metabolism genes. Recent data suggest that HIF-P4H inhibition has a therapeutic role beyond anemia in cardiac ischemia, obesity and metabolic dysfunction, and atherosclerosis...
November 8, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27825361/cancer-stem-cell-metabolism-a-potential-target-for-cancer-therapy
#14
REVIEW
Abhijeet Deshmukh, Kedar Deshpande, Frank Arfuso, Philip Newsholme, Arun Dharmarajan
Cancer Stem cells (CSCs) are a unipotent cell population present within the tumour cell mass. CSCs are known to be highly chemo-resistant, and in recent years, they have gained intense interest as key tumour initiating cells that may also play an integral role in tumour recurrence following chemotherapy. Cancer cells have the ability to alter their metabolism in order to fulfil bio-energetic and biosynthetic requirements. They are largely dependent on aerobic glycolysis for their energy production and also are associated with increased fatty acid synthesis and increased rates of glutamine utilisation...
November 8, 2016: Molecular Cancer
https://www.readbyqxmd.com/read/27818078/functional-and-genomic-architecture-of-borrelia-burgdorferi-induced-cytokine-responses-in-humans
#15
Marije Oosting, Mariska Kerstholt, Rob Ter Horst, Yang Li, Patrick Deelen, Sanne Smeekens, Martin Jaeger, Ekta Lachmandas, Hedwig Vrijmoeth, Mihaela Lupse, Mirela Flonta, Robert A Cramer, Bart Jan Kullberg, Vinod Kumar, Ramnik Xavier, Cisca Wijmenga, Mihai G Netea, Leo A B Joosten
Despite the importance of immune variation for the symptoms and outcome of Lyme disease, the factors influencing cytokine production during infection with the causal pathogen Borrelia burgdorferi remain poorly understood. Borrelia infection-induced monocyte- and T cell-derived cytokines were profiled in peripheral blood from two healthy human cohorts of Western Europeans from the Human Functional Genomics Project. Both non-genetic and genetic host factors were found to influence Borrelia-induced cytokine responses...
November 1, 2016: Cell Host & Microbe
https://www.readbyqxmd.com/read/27804847/the-warburg-effect-and-the-hallmarks-of-cancer
#16
Laurent Schwartz, Claudiu T Supuran, Khalid O Alfarouk
It is a longstanding debate whether cancer is one disease or a set of very diverse diseases. The goal of this paper is to suggest strongly that most (if not all) the hallmarks of cancer could be the consequence of the Warburg's effect. As a result of the metabolic impairment of the oxidative phosphorylation, there is a decrease in ATP concentration. To compensate the reduced energy yield, there is massive glucose uptake, anaerobic glycolysis, with an up-regulation of the Pentose Phosphate Pathway resulting in increased biosynthesis leading to increased cell division and local pressure...
October 31, 2016: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/27799347/unexpected-function-of-the-phagocyte-nadph-oxidase-in-supporting-hyperglycolysis-in-stimulated-neutrophils-key-role-of-6-phosphofructo-2-kinase
#17
Athan Baillet, Marc-André Hograindleur, Jamel El Benna, Alexei Grichine, Sylvie Berthier, Françoise Morel, Marie-Hélène Paclet
The phagocyte NADPH oxidase 2 (Nox2) is an enzymatic complex that is involved in innate immunity, notably via its capacity to produce toxic reactive oxygen species. Recently, a proteomic analysis of the constitutively active Nox2 complex, isolated from neutrophil fractions, highlighted the presence of 6-phosphofructo-2-kinase (PFK-2). The purpose of this work was to study the relationship between PFK-2 and NADPH oxidase in neutrophils. Data have underlined a specific association of the active phosphorylated form of PFK-2 with Nox2 complex in stimulated neutrophils...
October 31, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27797973/integrative-systemic-and-local-metabolomics-with-impact-on-survival-in-high-grade-serous-ovarian-cancer
#18
Anna Bachmayr-Heyda, Stefanie Aust, Katharina Auer, Samuel M Meier, Klaus G Schmetterer, Sabine Dekan, Christopher Gerner, Dietmar Pils
PURPOSE: Cancer metabolism is characterized by alterations including aerobic glycolysis, oxidative phosphorylation, and need of fuels and building blocks. EXPERIMENTAL DESIGN: Targeted metabolomics of pre-operative and follow-up sera, ascites, and tumor tissues, RNA sequencing of isolated tumor cells, local and systemic chemokine and local immune cell infiltration data from up to 65 high grade serous ovarian cancer patients and 62 healthy controls were correlated to overall survival and integrated in a Systems Medicine manner...
October 19, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27795296/phd2-is-a-regulator-for-glycolytic-reprogramming-in-macrophages
#19
Annemarie Guentsch, Angelika Beneke, Lija Swain, Katja Farhat, Shunmugam Nagarajan, Ben Wielockx, Kaamini Raithatha, Jan Dudek, Peter Rehling, Anke Zieseniss, Aline Jatho, Mei Chong, Celio X C Santos, Ajay M Shah, Dörthe M Katschinski
The prolyl-4-hydroxylase domain (PHD) enzymes are regarded as the molecular oxygen sensors. There is an interplay between oxygen availability and cellular metabolism, which in turn has significant effects on the functionality of innate immune cells like macrophages. If and how PHDs affect macrophage metabolism however is enigmatic. We hypothesized that via manipulation of PHD2 macrophage metabolism and function can be controlled. We characterized the metabolic phenotype of PHD2-deficient RAW cells and primary PHD2 knock out bone marrow derived macrophages (BMDM)...
October 17, 2016: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/27791989/stimulation-of-the-toll-like-receptor-3-promotes-metabolic-reprogramming-in-head-and-neck-carcinoma-cells
#20
Mathieu Veyrat, Sylvère Durand, Marion Classe, Tanja Matijevic Glavan, Natalie Oker, Nikiforos-Ioannis Kapetanakis, Xiaojun Jiang, Aurore Gelin, Philippe Herman, Odile Casiraghi, David Zagzag, David Enot, Pierre Busson, Benjamin Vérillaud
In this study, a possible link between the innate immune recognition receptor TLR3 and metabolic reprogramming in Head and Neck carcinoma (HNC) cells was investigated. The effects of TLR3 stimulation/knock-down were assessed under several culture conditions in 4 HNC cell-lines by cell growth assays, targeted metabolomics, and glycolysis assays based on time-resolved analysis of proton release (Seahorse analyzer). The stimulation of TLR3 by its synthetic agonist Poly(A:U) resulted in a faster growth of HNC cells under low foetal calf serum conditions...
October 25, 2016: Oncotarget
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