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Immune glycolysis

Siroon Bekkering, Inge van den Munckhof, Tim Nielen, Evert Lamfers, Charles Dinarello, Joost Rutten, Jacqueline de Graaf, Leo A B Joosten, Mihai G Netea, Marc E R Gomes, Niels P Riksen
BACKGROUND AND AIMS: We have recently reported that monocytes can undergo functional and transcriptional reprogramming towards a long-term pro-inflammatory phenotype after brief in vitro exposure to atherogenic stimuli such as oxidized LDL. This process is termed 'trained immunity', and is mediated by epigenetic remodeling and a metabolic switch towards increased aerobic glycolysis. We hypothesize that trained immunity contributes to atherogenesis. Therefore, we investigated the inflammatory phenotype and epigenetic remodeling of monocytes from patients with and without established atherosclerosis...
October 12, 2016: Atherosclerosis
Stanley Ching-Cheng Huang, Amber M Smith, Bart Everts, Marco Colonna, Erika L Pearce, Joel D Schilling, Edward J Pearce
Macrophage activation status is intrinsically linked to metabolic remodeling. Macrophages stimulated by interleukin 4 (IL-4) to become alternatively (or, M2) activated increase fatty acid oxidation and oxidative phosphorylation; these metabolic changes are critical for M2 activation. Enhanced glucose utilization is also characteristic of the M2 metabolic signature. Here, we found that increased glucose utilization is essential for M2 activation. Increased glucose metabolism in IL-4-stimulated macrophages required the activation of the mTORC2 pathway, and loss of mTORC2 in macrophages suppressed tumor growth and decreased immunity to a parasitic nematode...
October 18, 2016: Immunity
Hailong Zhang, Liang Qiao, Xiaopeng Li, Yang Wan, Li Yang, Huijuan Wang
Lymph node metastasis is a decisive prognostic and therapeutic staging factor for colorectal cancer (CRC), which is one of the most prevalent types of cancer and a malignant tumor. The metabolic profiling of tissue samples from a large cohort of lymph node non‑metastatic CRC patients (n=73), lymph node metastatic CRC patients (n=52) and normal controls (n=41) was performed using 1H nuclear magnetic resonance (NMR) together with multivariate statistical analyses. Excellent separation was obtained between CRC patients and normal controls, and CRC patients were also perfectly classified according to lymph node metastasis...
October 14, 2016: Oncology Reports
Siroon Bekkering, Bastiaan A Blok, Leo A B Joosten, Niels P Riksen, Reinout van Crevel, Mihai G Netea
BACKGROUND: Innate immune memory or 'trained immunity' has recently been described as an important property of cells of the innate immune system. Due to the increased interest in this important new field of immunological investigation we sought to determine the optimal conditions for an in-vitro experimental protocol of monocyte training using three of the most commonly used training stimuli from the literature: β-glucan, the Bacille Calmette-Guérin (BCG) vaccine, and oxidized LDL (oxLDL)...
October 12, 2016: Clinical and Vaccine Immunology: CVI
Xue-Jiao Chang, Chao-Qun Zheng, Yu-Wei Wang, Chuang Meng, Xiao-Lu Xie, Hai-Peng Liu
Gradually increasing atmospheric CO2 partial pressure (pCO2) has caused an imbalance in carbonate chemistry and resulted in decreased seawater pH in marine ecosystems, termed seawater acidification. Anthropogenic seawater acidification is postulated to affect the physiology of many marine calcifying organisms. To understand the possible effects of seawater acidification on the proteomic responses of a marine crustacean brine shrimp (Artemia sinica) three groups of cysts were hatched and further raised in seawater at different pH levels (8...
October 7, 2016: Fish & Shellfish Immunology
Marc O Johnson, Peter J Siska, Diana C Contreras, Jeffrey C Rathmell
T cells have dramatic functional and proliferative shifts in the course of maintaining immune protection from pathogens and cancer. To support these changes, T cells undergo metabolic reprogramming upon stimulation and again after antigen clearance. Depending on the extrinsic cell signals, T cells can differentiate into functionally distinct subsets that utilize and require diverse metabolic programs. Effector T cells (Teff) enhance glucose and glutamine uptake, whereas regulatory T cells (Treg) do not rely on significant rates of glycolysis...
October 3, 2016: Seminars in Immunology
Rob J W Arts, Leo A B Joosten, Mihai G Netea
The classical view that only adaptive immunity can build immunological memory has recently been challenged. Both in organisms lacking adaptive immunity as well as in mammals, the innate immune system can adapt to mount an increased resistance to reinfection, a de facto innate immune memory termed trained immunity. Recent studies have revealed that rewiring of cellular metabolism induced by different immunological signals is a crucial step for determining the epigenetic changes underlying trained immunity. Processes such as a shift of glucose metabolism from oxidative phosphorylation to aerobic glycolysis, increased glutamine metabolism and cholesterol synthesis, play a crucial role in these processes...
September 26, 2016: Seminars in Immunology
Goodwin G Jinesh, Sharada Mokkapati, Keyi Zhu, Edwin E Morales
Pim kinases are being implicated in oncogenic process in various human cancers. Pim kinases primarily deal with three broad categories of functions such as tumorigenesis, protecting cells from apoptotic signals and evading immune attacks. Here in this review, we discuss the regulation of Pim kinases and their expression, and how these kinases defend cancer cells from therapeutic and immune attacks with special emphasis on how Pim kinases maintain their own expression during apoptosis and cellular transformation, defend mitochondria during apoptosis, defend cancer cells from immune attack, defend cancer cells from therapeutic attack, choose localization, self-regulation, activation of oncogenic transcription, metabolic regulation and so on...
November 2016: Apoptosis: An International Journal on Programmed Cell Death
G Gdynia
The German Nobel Prize winner Otto Warburg discovered the importance of glycolysis in cancer cells in the 1920s. Nearly one century later the inhibition of tumor glycolysis in cancer cells could literally be the Achilles Heel in cancer therapy. Surprisingly, we could show that Natural Killer (NK) cells pursue this strategy. They employ specific metabolic weapons to eliminate cancer cells by targeting tumor glycolysis. In colon cancer cells a specifically modified form of high mobility group box 1 (HMGB1) protein released by NK cells induced a previously unknown form of cell death...
September 14, 2016: Der Pathologe
Hu Zeng, Sivan Cohen, Cliff Guy, Sharad Shrestha, Geoffrey Neale, Scott A Brown, Caryn Cloer, Rigel J Kishton, Xia Gao, Ben Youngblood, Mytrang Do, Ming O Li, Jason W Locasale, Jeffrey C Rathmell, Hongbo Chi
Follicular helper T (Tfh) cells are crucial for germinal center (GC) formation and humoral adaptive immunity. Mechanisms underlying Tfh cell differentiation in peripheral and mucosal lymphoid organs are incompletely understood. We report here that mTOR kinase complexes 1 and 2 (mTORC1 and mTORC2) are essential for Tfh cell differentiation and GC reaction under steady state and after antigen immunization and viral infection. Loss of mTORC1 and mTORC2 in T cells exerted distinct effects on Tfh cell signature gene expression, whereas increased mTOR activity promoted Tfh responses...
September 20, 2016: Immunity
Xiang Li, Xingqi Wang, Hezhong Jiang, Guohui Zhang, Rui Tan, Yang Sun, Xuefeng Wu, Renxiang Tan, Qiang Xu
An immunosuppressant with fewer adverse effects is still urgently needed for increasing numbers of patients suffering from allergic contact dermatitis. In the present study, we aimed to investigate the immunosuppressive activity of herpetol on T-lymphocytes in vitro and in vivo and explore its potential pharmacological mechanism. The results showed that herpetol could effectively inhibit the proliferation of activated T cells and reduce the production of pro-inflammatory cytokines at 5-20μM. Additionally, the ear swelling and inflammatory responses induced by picryl chloride were significantly ameliorated by herpetol at 20-40mg/kg...
August 30, 2016: International Immunopharmacology
P Fonseca, I Vardaki, A Occhionero, T Panaretakis
Extracellular vesicles have gained tremendous attention in the recent years as a novel mechanism of cell to cell communication. There are several types of extracellular vesicles, including exosomes, microvesicles, exosome, like vesicles, apoptotic bodies that differ mainly in the mechanism of biogenesis and secretion. The most well studied type of extracellular vesicles are the exosomes which are endosome-derived vesicles with a diameter of 50-150nm and enriched in ESCRT proteins including Alix, TSG101, Hsp70, and tetraspanins...
2016: International Review of Cell and Molecular Biology
Sarah E Corcoran, Luke A J O'Neill
HIF1α is a common component of pathways involved in the control of cellular metabolism and has a role in regulating immune cell effector functions. Additionally, HIF1α is critical for the maturation of dendritic cells and for the activation of T cells. HIF1α is induced in LPS-activated macrophages, where it is critically involved in glycolysis and the induction of proinflammatory genes, notably Il1b. The mechanism of LPS-stimulated HIF1α induction involves succinate, which inhibits prolyl hydroxylases (PHDs)...
October 3, 2016: Journal of Clinical Investigation
Hui Jiang, Hengfei Shi, Man Sun, Yafeng Wang, Qingzhou Meng, Panpan Guo, Yanlan Cao, Jiong Chen, Xiang Gao, Erguang Li, Jianghuai Liu
Signaling by viral nucleic acids and subsequently by type I IFN is central to antiviral innate immunity. These signaling events are also likely to engage metabolic changes in immune and nonimmune cells to support antiviral defense. In this study, we show that cytosolic viral recognition, by way of secondary IFN signaling, leads to upregulation of glycolysis preferentially in macrophages. This metabolic switch involves induction of glycolytic activator 6-phosphofructose-2-kinase and fructose-2,6-bisphosphatase (PFKFB3)...
October 1, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Gang Wang, Xing-Li Fu, Jun-Jie Wang, Rui Guan, Xiang-Jun Tang
Glioblastoma multiforme is a common primary brain tumor, which exhibits an imbalance between glioma cell growth and glucose metabolism. Recent discoveries have found the multiple pathways and downstream genes are involved in the dysregulated metabolic pathway allows tumor to start and progress, which is critical to the patients with glioblastoma associated with significant systemic and immunosuppression. Moreover, immune microenvironment is considered a major obstacle to generating an effective antitumor immune response...
May 12, 2016: Current Cancer Drug Targets
Mahin Khatami
Longevity and accumulation of multiple context-dependent signaling pathways of long-standing inflammation (antigen-load or oxidative stress) are the results of decreased/altered regulation of immunity and loss of control switch mechanisms that we defined as Yin and Yang of acute inflammation or immune surveillance. Chronic inflammation is initiated by immune disruptors-induced progressive changes in physiology and function of susceptible host tissues that lead to increased immune suppression and multistep disease processes including carcinogenesis...
December 2016: Clinical and Translational Medicine
Frederick Goetz, Sara E Smith, Giles Goetz, Cheryl A Murphy
BACKGROUND: The sea lamprey (Petromyzon marinus) is a jawless vertebrate that parasitizes fish as an adult and, with overfishing, was responsible for the decline in lake trout (Salvelinus namaycush) populations in the Great Lakes. While laboratory studies have looked at the rates of wounding on various fish hosts, there have been few investigations on the physiological effects of lamprey wounding on the host. In the current study, two morphotypes of lake trout, leans and siscowets, were parasitized in the laboratory by sea lampreys and the liver transcriptomes of parasitized and nonparasitized fish were analyzed by RNA-seq (DESeq2 and edgeR) to determine which genes and gene pathways (Ingenuity Pathway Analysis) were altered by lamprey parasitism...
2016: BMC Genomics
Teresa W-M Fan, Marc O Warmoes, Qiushi Sun, Huan Song, Jadwiga Turchan-Cholewo, Jeremiah T Martin, Angela Mahan, Richard M Higashi, Andrew N Lane
Cancer and stromal cell metabolism is important for understanding tumor development, which highly depends on the tumor microenvironment (TME). Cell or animal models cannot recapitulate the human TME. We have developed an ex vivo paired cancerous (CA) and noncancerous (NC) human lung tissue approach to explore cancer and stromal cell metabolism in the native human TME. This approach enabled full control of experimental parameters and acquisition of individual patient's target tissue response to therapeutic agents while eliminating interferences from genetic and physiological variations...
July 2016: Cold Spring Harbor Molecular Case Studies
Terri N Iwata, Julita A Ramírez, Mark Tsang, Heon Park, Daciana H Margineantu, David M Hockenbery, Brian M Iritani
Mechanistic target of rapamycin (mTOR) is a serine-threonine kinase that coordinates nutrient and growth factor availability with cellular growth, division, and differentiation. Studies examining the roles of mTOR signaling in immune function revealed critical roles for mTOR in regulating T cell differentiation and function. However, few studies have investigated the roles of mTOR in early B cell development. In this study, we found that mTOR is highly activated during the pro- and pre-B stages of mouse B cell development...
September 15, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
Christoph Herbel, Nikolaos Patsoukis, Kankana Bardhan, Pankaj Seth, Jessica D Weaver, Vassiliki A Boussiotis
Conversion of normal cells to cancer is accompanied with changes in their metabolism. During this conversion, cell metabolism undergoes a shift from oxidative phosphorylation to aerobic glycolysis, also known as Warburg effect, which is a hallmark for cancer cell metabolism. In cancer cells, glycolysis functions in parallel with the TCA cycle and other metabolic pathways to enhance biosynthetic processes and thus support proliferation and growth. Similar metabolic features are observed in T cells during activation but, in contrast to cancer, metabolic transitions in T cells are part of a physiological process...
December 2016: Clinical and Translational Medicine
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