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Immune glycolysis

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https://www.readbyqxmd.com/read/28742108/fasting-metabolism-modulates-the-interleukin-12-interleukin-10-cytokine-axis
#1
Johannes J Kovarik, Elisabeth Kernbauer, Markus A Hölzl, Johannes Hofer, Guido A Gualdoni, Klaus G Schmetterer, Fitore Miftari, Yury Sobanov, Anastasia Meshcheryakova, Diana Mechtcheriakova, Nadine Witzeneder, Georg Greiner, Anna Ohradanova-Repic, Petra Waidhofer-Söllner, Marcus D Säemann, Thomas Decker, Gerhard J Zlabinger
A crucial role of cell metabolism in immune cell differentiation and function has been recently established. Growing evidence indicates that metabolic processes impact both, innate and adaptive immunity. Since a down-stream integrator of metabolic alterations, mammalian target of rapamycin (mTOR), is responsible for controlling the balance between pro-inflammatory interleukin (IL)-12 and anti-inflammatory IL-10, we investigated the effect of upstream interference using metabolic modulators on the production of pro- and anti-inflammatory cytokines...
2017: PloS One
https://www.readbyqxmd.com/read/28732079/lmp1-mediated-glycolysis-induces-myeloid-derived-suppressor-cell-expansion-in-nasopharyngeal-carcinoma
#2
Ting-Ting Cai, Shu-Biao Ye, Yi-Na Liu, Jia He, Qiu-Yan Chen, Hai-Qiang Mai, Chuan-Xia Zhang, Jun Cui, Xiao-Shi Zhang, Pierre Busson, Yi-Xin Zeng, Jiang Li
Myeloid-derived suppressor cells (MDSCs) are expanded in tumor microenvironments, including that of Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC). The link between MDSC expansion and EBV infection in NPC is unclear. Here, we show that EBV latent membrane protein 1 (LMP1) promotes MDSC expansion in the tumor microenvironment by promoting extra-mitochondrial glycolysis in malignant cells, which is a scenario for immune escape initially suggested by the frequent, concomitant detection of abundant LMP1, glucose transporter 1 (GLUT1) and CD33+ MDSCs in tumor sections...
July 21, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28713392/il-15-harnesses-pro-inflammatory-function-of-temra-cd8-in-kidney-transplant-recipients
#3
Gaëlle Tilly, Tra-My Doan-Ngoc, Michelle Yap, Aurélie Caristan, Lola Jacquemont, Richard Danger, Marion Cadoux, Sarah Bruneau, Magali Giral, Pierrick Guerif, Bryan Nicol, Alexandra Garcia, David-Axel Laplaud, Sophie Brouard, Claire Pecqueur Hellman, Nicolas Degauque
The involvement of TEMRA CD8 is evident in a large array of immunological conditions ranging from auto- to allo-immunity. Nevertheless, the factors leading to their accumulation and activation remain ill-defined and, efficient therapeutics to control their inflammatory response is lacking. Here, we show that IL-15-stimulated TEMRA from kidney-transplant (KT) recipients promote inflammation by inducing the expression of CX3CL1 by endothelial cells in an IFN-γ- and TNF-α-dependent manner. The responsiveness of TEMRA to IL-15 is not restricted to chronic stimulation, as TEMRA from healthy volunteers respond earlier and faster when compared to effector memory (EM)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28708972/uv-irradiation-of-skin-enhances-glycolytic-flux-and-reduces-migration-capabilities-in-bone-marrow-differentiated-dendritic-cells
#4
Terence A McGonigle, Kevin N Keane, Simon Ghaly, Kim W Carter, Denise Anderson, Naomi M Scott, Helen S Goodridge, Amy Dwyer, Eloise Greenland, Fiona J Pixley, Philip Newsholme, Prue H Hart
A systemic immunosuppression follows UV irradiation of the skin of humans and mice. In this study, dendritic cells (DCs) differentiating from the bone marrow of UV-irradiated mice had a reduced ability to migrate toward the chemokine (C-C motif) ligand 21. Fewer DCs also accumulated in the peritoneal cavity of UV-chimeric mice (ie, mice transplanted with bone marrow from UV-irradiated mice) after injection of an inflammatory stimulus into that site. We hypothesized that different metabolic states underpin altered DC motility...
July 11, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28683296/inflammasomes-on-the-crossroads-of-innate-immune-recognition-and-metabolic-control
#5
REVIEW
Tomasz Próchnicki, Eicke Latz
Inflammasomes are protein complexes formed upon encounter of microbial or damage-associated stimuli. The main output of inflammasome assembly is activation of caspase-1, a protease involved in both pro-inflammatory and host-protective responses. Defined bacterial or viral ligands have been identified for the inflammasome-forming receptors AIM2, NLRP1, and NLRC4. The signals activating other inflammasomes, NLRP3, NLRP6, and pyrin, are less well understood. Recent studies implicated several low-molecular-weight compounds traditionally linked to metabolism, not immunity, in modulation of inflammasome signaling...
July 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28674530/endoplasmic-reticulum-stress-sensor-ire1%C3%AE-enhances-il-23-expression-by-human-dendritic-cells
#6
Saioa Márquez, José Javier Fernández, Eli Terán-Cabanillas, Carmen Herrero, Sara Alonso, Alicia Azogil, Olimpio Montero, Takao Iwawaki, Juan R Cubillos-Ruiz, Nieves Fernández, Mariano Sánchez Crespo
Human monocyte-derived dendritic cells (DCs) exposed to pathogen-associated molecular patterns (PAMPs) undergo bioenergetic changes that influence the immune response. We found that stimulation with PAMPs enhanced glycolysis in DCs, whereas oxidative phosphorylation remained unaltered. Glucose starvation and the hexokinase inhibitor 2-deoxy-d-glucose (2-DG) modulated cytokine expression in stimulated DCs. Strikingly, IL23A was markedly induced upon 2-DG treatment, but not during glucose deprivation. Since 2-DG can also rapidly inhibit protein N-glycosylation, we postulated that this compound could induce IL-23 in DCs via activation of the endoplasmic reticulum (ER) stress response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28661041/metabolic-control-of-type-2-immunity
#7
REVIEW
Leonard R Pelgrom, Bart Everts
Type 2 immune responses play key roles in protection against parasitic worm infections, whole-body metabolic homeostasis, wound healing and the development of allergies. As a result, there is considerable interest in understanding the pathways that regulate type 2 immunity in order to identify strategies of targeting and controlling these responses. In recent years, it has become increasingly clear that the functional properties of immune cells, including those involved in type 2 immune responses, are dependent on the engagement of specific metabolic pathways such as aerobic glycolysis and fatty acid oxidation (FAO)...
June 29, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28634388/mito-xenophagic-killing-of-bacteria-is-coordinated-by-a-metabolic-switch-in-dendritic-cells
#8
Nadine Radomski, Danny Kägebein, Elisabeth Liebler-Tenorio, Axel Karger, Elke Rufer, Birke Andrea Tews, Stefanie Nagel, Rebekka Einenkel, Anne Müller, Annica Rebbig, Michael R Knittler
Chlamydiae are bacterial pathogens that grow in vacuolar inclusions. Dendritic cells (DCs) disintegrate these compartments, thereby eliminating the microbes, through auto/xenophagy, which also promotes chlamydial antigen presentation via MHC I. Here, we show that TNF-α controls this pathway by driving cytosolic phospholipase (cPLA)2-mediated arachidonic acid (AA) production. AA then impairs mitochondrial function, which disturbs the development and integrity of these energy-dependent parasitic inclusions, while a simultaneous metabolic switch towards aerobic glycolysis promotes DC survival...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28621843/metabolic-reprogramming-in-the-tumour-microenvironment-a-hallmark-shared-by-cancer-cells-and-t-lymphocytes
#9
REVIEW
Katrina E Allison, Brenda L Coomber, Byram W Bridle
Altered metabolism is a hallmark of cancers, including shifting oxidative phosphorylation to glycolysis and upregulating glutaminolysis to divert carbon sources into biosynthetic pathways that promote proliferation and survival. Therefore, metabolic inhibitors represent promising anti-cancer drugs. However, T cells must rapidly divide and survive in harsh microenvironments to mediate anti-cancer effects. Metabolic profiles of cancer cells and activated T lymphocytes are similar, raising the risk of metabolic inhibitors impairing the immune system...
June 16, 2017: Immunology
https://www.readbyqxmd.com/read/28615443/control-of-immune-mediated-pathology-via-the-aryl-hydrocarbon-receptor
#10
Michael A Wheeler, Veit Rothhammer, Francisco J Quintana
Genetic and environmental factors contribute to the development of immune-mediated diseases. While numerous genetic factors contributing to autoimmunity have been identified in recent years, our knowledge on environmental factors contributing to the pathogenesis of autoimmune diseases and the mechanisms involved is still limited. In this context, the diet, geographical location, environmental pollutants, as well as microbial metabolites have been shown to modulate autoimmune disease development. These environmental factors interact with cellular components of the immune system in distinct and defined ways and are capable of influencing immune responses at the transcriptional and protein level...
June 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28614802/mitochondrial-dysregulation-and-glycolytic-insufficiency-functionally-impair-cd8-t-cells-infiltrating-human-renal-cell-carcinoma
#11
Peter J Siska, Kathryn E Beckermann, Frank M Mason, Gabriela Andrejeva, Allison R Greenplate, Adam B Sendor, Yun-Chen J Chiang, Armando L Corona, Lelisa F Gemta, Benjamin G Vincent, Richard C Wang, Bumki Kim, Jiyong Hong, Chiu-Lan Chen, Timothy N Bullock, Jonathan M Irish, W Kimryn Rathmell, Jeffrey C Rathmell
Cancer cells can inhibit effector T cells (Teff) through both immunomodulatory receptors and the impact of cancer metabolism on the tumor microenvironment. Indeed, Teff require high rates of glucose metabolism, and consumption of essential nutrients or generation of waste products by tumor cells may impede essential T cell metabolic pathways. Clear cell renal cell carcinoma (ccRCC) is characterized by loss of the tumor suppressor von Hippel-Lindau (VHL) and altered cancer cell metabolism. Here, we assessed how ccRCC influences the metabolism and activation of primary patient ccRCC tumor infiltrating lymphocytes (TIL)...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28611773/fatty-acid-oxidation-compensates-for-lipopolysaccharide-induced-warburg-effect-in-glucose-deprived-monocytes
#12
Nora Raulien, Kathleen Friedrich, Sarah Strobel, Stefan Rubner, Sven Baumann, Martin von Bergen, Antje Körner, Martin Krueger, Manuela Rossol, Ulf Wagner
Monocytes enter sites of microbial or sterile inflammation as the first line of defense of the immune system and initiate pro-inflammatory effector mechanisms. We show that activation with bacterial lipopolysaccharide (LPS) induces them to undergo a metabolic shift toward aerobic glycolysis, similar to the Warburg effect observed in cancer cells. At sites of inflammation, however, glucose concentrations are often drastically decreased, which prompted us to study monocyte function under conditions of glucose deprivation and abrogated Warburg effect...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28611673/reversing-egfr-mediated-immunoescape-by-targeted-monoclonal-antibody-therapy
#13
REVIEW
Fernando Concha-Benavente, Robert L Ferris
Uncontrolled growth is a signature of carcinogenesis, in part mediated by overexpression or overstimulation of growth factor receptors. The epidermal growth factor receptor (EGFR) mediates activation of multiple oncogenic signaling pathways and escape from recognition by the host immune system. We discuss how EGFR signaling downregulates tumor antigen presentation, upregulates suppressive checkpoint receptor ligand programmed death ligand (PD-L1), induces secretion of inhibitory molecules such as transforming growth factor beta (TGFβ) and reprograms the metabolic pathways in cancer cells to upregulate aerobic glycolysis and lactate secretion that ultimately lead to impaired cellular immunity mediated by natural killer (NK) cell and cytotoxic T lymphocytes (CTL)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28604752/tumor-cell-derived-lactate-induces-taz-dependent-upregulation-of-pd-l1-through-gpr81-in-human-lung-cancer-cells
#14
J Feng, H Yang, Y Zhang, H Wei, Z Zhu, B Zhu, M Yang, W Cao, L Wang, Z Wu
The clinical success of immunotherapy that inhibits the negative immune regulatory pathway programmed cell death protein 1/PD-1 ligand (PD-1/PD-L1) has initiated a new era in the treatment of metastatic cancer. PD-L1 expression is upregulated in many solid tumors including lung cancer and functions predominantly in lactate-enriched tumor microenvironments. Here, we provided evidence for PD-L1 induction in response to lactate stimulation in lung cancer cells. Lactate-induced PD-L1 induction was mediated by its receptor GPR81...
June 12, 2017: Oncogene
https://www.readbyqxmd.com/read/28600802/mtorc1-and-mtorc2-as-regulators-of-cell-metabolism-in-immunity
#15
REVIEW
Monika Linke, Stephanie Deborah Fritsch, Nyamdelger Sukhbaatar, Markus Hengstschläger, Thomas Weichhart
The mechanistic target of rapamycin (mTOR) pathway is an evolutionarily conserved signaling pathway that senses intra- and extracellular nutrients, growth factors, and pathogen-associated molecular patterns to regulate the function of innate and adaptive immune cell populations. In this Review, we focus on the role of the mTOR complex 1 (mTORC1) and mTORC2 in the regulation of the cellular energy metabolism of these immune cells to regulate and support immune responses. In this regard, mTORC1 and mTORC2 generally promote an anabolic response by stimulating protein synthesis, glycolysis, mitochondrial functions, and lipid synthesis to influence proliferation and survival, effector and memory responses, innate training and tolerance as well as hematopoietic stem cell maintenance and differentiation...
June 10, 2017: FEBS Letters
https://www.readbyqxmd.com/read/28592803/first-comprehensive-proteome-analysis-of-lysine-crotonylation-in-seedling-leaves-of-nicotiana-tabacum
#16
Hangjun Sun, Xiaowei Liu, Fangfang Li, Wei Li, Jing Zhang, Zhixin Xiao, Lili Shen, Ying Li, Fenglong Wang, Jinguang Yang
Histone crotonylation is a new lysine acylation type of post-translational modification (PTM) enriched at active gene promoters and potential enhancers in yeast and mammalian cells. However, lysine crotonylation in nonhistone proteins and plant cells has not yet been studied. In the present study, we performed a global crotonylation proteome analysis of Nicotiana tabacum (tobacco) using high-resolution LC-MS/MS coupled with highly sensitive immune-affinity purification. A total of 2044 lysine modification sites distributed on 637 proteins were identified, representing the most abundant lysine acylation proteome reported in the plant kingdom...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28588149/tumor-metabolic-features-identified-by-fdg-pet-correlates-with-gene-networks-of-immune-cell-microenvironment-in-head-and-neck-cancer
#17
Kwon Joong Na, Hongyoon Choi
The importance of FDG PET in imaging head and neck squamous cell carcinoma (HNSCC) has grown in recent decades. Since PET has prognostic values, and provides functional and molecular information in HNSCC, the genetic and biologic backgrounds associated with PET parameters are of great interests. Here, as a systems biology approach, we aimed to investigate gene networks associated with tumor metabolism and their biological function using RNA sequence and FDG PET data. Methods: Using RNA sequence data of HNSCC downloaded from TCGA data portal, we constructed gene coexpression network...
June 6, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28580955/ndfip1-restricts-mtorc1-signalling-and-glycolysis-in-regulatory-t-cells-to-prevent-autoinflammatory-disease
#18
Awo Akosua Kesewa Layman, Guoping Deng, Claire E O'Leary, Samuel Tadros, Rajan M Thomas, Joseph M Dybas, Emily K Moser, Andrew D Wells, Nicolai M Doliba, Paula M Oliver
Foxp3(+) T regulatory (Treg) cells suppress immune cell activation and establish normal immune homeostasis. How Treg cells maintain their identity is not completely understood. Here we show that Ndfip1, a coactivator of Nedd4-family E3 ubiquitin ligases, is required for Treg cell stability and function. Ndfip1 deletion in Treg cells results in autoinflammatory disease. Ndfip1-deficient Treg cells are highly proliferative and are more likely to lose Foxp3 expression to become IL-4-producing TH2 effector cells...
June 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28580131/recent-insights-into-the-implications-of-metabolism-in-plasmacytoid-dendritic-cell-innate-functions-potential-ways-to-control-these-functions
#19
REVIEW
Philippe Saas, Alexis Varin, Sylvain Perruche, Adam Ceroi
There are more and more data concerning the role of cellular metabolism in innate immune cells, such as macrophages or conventional dendritic cells. However, few data are available currently concerning plasmacytoid dendritic cells (PDC), another type of innate immune cells. These cells are the main type I interferon (IFN) producing cells, but they also secrete other pro-inflammatory cytokines (e.g., tumor necrosis factor or interleukin [IL]-6) or immunomodulatory factors (e.g., IL-10 or transforming growth factor-β)...
2017: F1000Research
https://www.readbyqxmd.com/read/28572631/understanding-the-mechanisms-of-dormancy-in-an-invasive-alien-sycamore-lace-bug-corythucha-ciliata-through-transcript-and-metabolite-profiling
#20
Feng-Qi Li, Ning-Ning Fu, Cheng Qu, Ran Wang, Yi-Hua Xu, Chen Luo
The sycamore lace bug, Corythucha ciliata, is a pest of sycamore trees. In China, it is found in the most northern border where it has been known to become dormant during harsh winters. But the molecular and metabolic basis for dormancy in this insect is still unknown. In this study, we analyzed the transcript and metabolite profiles of this bug to identify key genes and metabolites that are significantly regulated during dormancy in adult females and males. In total, 149 differentially expressed genes (DEGs) were significantly up-regulated and 337 DEGs were significantly down-regulated in dormant adults (both females and males)...
June 1, 2017: Scientific Reports
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