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Immune glycolysis

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https://www.readbyqxmd.com/read/28634388/mito-xenophagic-killing-of-bacteria-is-coordinated-by-a-metabolic-switch-in-dendritic-cells
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/28557618/microenvironment-tumor-metabolic-interactions-highlighted-by-qmsi-application-to-the-tryptophan-kynurenine-pathway-in-immuno-oncology
#14
Rima Ait-Belkacem, Vanesa Bol, Gregory Hamm, Florence Schramme, Benoit Van Den Eynde, Lauranne Poncelet, Fabien Pamelard, Jonathan Stauber, Bruno Gomes
Inhibition of NK and effector T-cell functions and activation of regulatory cell populations are the main immunosuppressive effects of indoleamine-2,3-dioxygenase1 (IDO1). By converting tryptophan (Trp) into kynurenine (Kyn), IDO1 is involved in the immune response homeostasis, and its dysregulated expression is described in immune-related pathologies, as tumors that hijack it to evade immune destruction. Thereby, IDO1 inhibitors are being developed to stimulate antitumor immune responses. Existing and standard quantitation methods of IDO1 substrate and metabolite(s) are based on the total level of Trp and its metabolites determined by liquid chromatography tandem mass spectrometry analysis in human plasma, cerebrospinal fluid, and brain...
May 1, 2017: SLAS Discovery
https://www.readbyqxmd.com/read/28555668/glucose-represses-dendritic-cell-induced-t-cell-responses
#15
Simon J Lawless, Nidhi Kedia-Mehta, Jessica F Walls, Ryan McGarrigle, Orla Convery, Linda V Sinclair, Maria N Navarro, James Murray, David K Finlay
Glucose and glycolysis are important for the proinflammatory functions of many immune cells, and depletion of glucose in pathological microenvironments is associated with defective immune responses. Here we show a contrasting function for glucose in dendritic cells (DCs), as glucose represses the proinflammatory output of LPS-stimulated DCs and inhibits DC-induced T-cell responses. A glucose-sensitive signal transduction circuit involving the mTOR complex 1 (mTORC1), HIF1α and inducible nitric oxide synthase (iNOS) coordinates DC metabolism and function to limit DC-stimulated T-cell responses...
May 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28549626/cell-biology-metabolic-crosstalk-in-glioma
#16
REVIEW
Alison Colquhoun
The renewed interest in cancer metabolism in recent years has been fuelled by the identification of the involvement of key oncogenes and tumour suppressor genes in the control of metabolic pathways. Many of these alterations lead to dramatic changes in bioenergetics, biosynthesis and redox balance within tumour cells. The complex relationship between tumour cell metabolism and the tumour microenvironment has turned this field of biochemistry and cell biology into a challenging and exciting area for study. In the case of gliomas the involvement of altered metabolic pathways including glycolysis, oxidative phosphorylation and glutaminolysis are pointing the way to new possibilities for treatment...
May 23, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28545737/microrna-146a-governs-fibroblast-activation-and-joint-pathology-in-arthritis
#17
Victoria Saferding, Antonia Puchner, Eliana Goncalves-Alves, Melanie Hofmann, Michael Bonelli, Julia S Brunner, Emine Sahin, Birgit Niederreiter, Silvia Hayer, Hans P Kiener, Elisa Einwallner, Ramzi Nehmar, Raphael Carapito, Philippe Georgel, Marije I Koenders, Mark Boldin, Gernot Schabbauer, Mariola Kurowska-Stolarska, Günter Steiner, Josef S Smolen, Kurt Redlich, Stephan Blüml
Synovial fibroblasts are key cells orchestrating the inflammatory response in arthritis. Here we demonstrate that loss of miR-146a, a key epigenetic regulator of the innate immune response, leads to increased joint destruction in a TNF-driven model of arthritis by specifically regulating the behavior of synovial fibroblasts. Absence of miR-146a in synovial fibroblasts display a highly deregulated gene expression pattern and enhanced proliferation in vitro and in vivo. Deficiency of miR-146a induces deregulation of tumor necrosis factor (TNF) receptor associated factor 6 (TRAF6) in synovial fibroblasts, leading to increased proliferation...
May 22, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28544771/quantitative-proteomic-analysis-of-host-epithelial-cells-infected-by-salmonella-enterica-serovar-typhimurium
#18
Linlu Qi, Mo Hu, Jiaqi Fu, Yanhua Liu, Mei Wu, Kaiwen Yu, Xiaoyun Liu
Systems-level analyses have the capability to offer new insight into host-pathogen interactions on the molecular level. Using Salmonella infection of host epithelial cells as a model system, we previously analyzed intracellular bacterial proteome as a window into pathogens' adaptations to their host environment (Infect. Immun. 2015; J. Proteome Res. 2017). Herein we extended our efforts to quantitatively examine protein expression of host cells during infection. In total, we identified more than 5,000 proteins with 194 differentially regulated proteins upon bacterial infection...
May 25, 2017: Proteomics
https://www.readbyqxmd.com/read/28542224/is-spaceflight-induced-immune-dysfunction-linked-to-systemic-changes-in-metabolism
#19
Michael J Pecaut, Xiao Wen Mao, Denise L Bellinger, Karen R Jonscher, Louis S Stodieck, Virginia L Ferguson, Ted A Bateman, Robert P Mohney, Daila S Gridley
The Space Shuttle Atlantis launched on its final mission (STS-135) on July 8, 2011. After just under 13 days, the shuttle landed safely at Kennedy Space Center (KSC) for the last time. Female C57BL/6J mice flew as part of the Commercial Biomedical Testing Module-3 (CBTM-3) payload. Ground controls were maintained at the KSC facility. Subsets of these mice were made available to investigators as part of NASA's Bio-specimen Sharing Program (BSP). Our group characterized cell phenotype distributions and phagocytic function in the spleen, catecholamine and corticosterone levels in the adrenal glands, and transcriptomics/metabolomics in the liver...
2017: PloS One
https://www.readbyqxmd.com/read/28541512/the-interplay-between-metabolic-remodeling-and-immune-regulation-in-glioblastoma
#20
Pravin Kesarwani, Shiva Kant, Antony Prabhu, Prakash Chinnaiyan
The fields of tumor metabolism and immune oncology have both independently received considerable attention over the last several years. The majority of research in tumor metabolism has largely focused on the Warburg effect and its resulting biologic consequences, including energy and macromolecule production. However, recent investigations have identified elegant, multifaceted strategies by which alterations in tumor metabolism can also contribute towards a potent tolerogenic immune environment. One of the most notable is increased tryptophan metabolism through activation of the indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO) pathways...
May 25, 2017: Neuro-oncology
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