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Immune glycolysis

Thenappan Thenappan, Mark L Ormiston, John J Ryan, Stephen L Archer
Pulmonary hypertension is defined as a resting mean pulmonary artery pressure of 25 mm Hg or above. This review deals with pulmonary arterial hypertension (PAH), a type of pulmonary hypertension that primarily affects the pulmonary vasculature. In PAH, the pulmonary vasculature is dynamically obstructed by vasoconstriction, structurally obstructed by adverse vascular remodeling, and pathologically non-compliant as a result of vascular fibrosis and stiffening. Many cell types are abnormal in PAH, including vascular cells (endothelial cells, smooth muscle cells, and fibroblasts) and inflammatory cells...
March 14, 2018: BMJ: British Medical Journal
Xiang Zhang, Adil Mardinoglu, Leo A B Joosten, Jan A Kuivenhoven, Yang Li, Mihai G Netea, Albert K Groen
Immunity and cellular metabolism are tightly interconnected but it is not clear whether different pathogens elicit specific metabolic responses. To address this issue, we studied differential metabolic regulation in peripheral blood mononuclear cells (PBMCs) of healthy volunteers challenged by Candida albicans, Borrelia burgdorferi , lipopolysaccharide, and Mycobacterium tuberculosis in vitro . By integrating gene expression data of stimulated PBMCs of healthy individuals with the KEGG pathways, we identified both common and pathogen-specific regulated pathways depending on the time of incubation...
2018: Frontiers in Physiology
Gerry Q Tonkin-Hill, Leily Trianty, Rintis Noviyanti, Hanh H T Nguyen, Boni F Sebayang, Daniel A Lampah, Jutta Marfurt, Simon A Cobbold, Janavi S Rambhatla, Malcolm J McConville, Stephen J Rogerson, Graham V Brown, Karen P Day, Ric N Price, Nicholas M Anstey, Anthony T Papenfuss, Michael F Duffy
Within the human host, the malaria parasite Plasmodium falciparum is exposed to multiple selection pressures. The host environment changes dramatically in severe malaria, but the extent to which the parasite responds to-or is selected by-this environment remains unclear. From previous studies, the parasites that cause severe malaria appear to increase expression of a restricted but poorly defined subset of the PfEMP1 variant, surface antigens. PfEMP1s are major targets of protective immunity. Here, we used RNA sequencing (RNAseq) to analyse gene expression in 44 parasite isolates that caused severe and uncomplicated malaria in Papuan patients...
March 12, 2018: PLoS Biology
Zengpeng Lv, Hao Fan, Beibei Zhang, Chao Ning, Kun Xing, Yuming Guo
Genistein (GEN) is a type of isoflavone mainly derived from soy products. In this experiment, we added 40 and 400 mg/kg GEN to the diet of laying broiler breeder hens to clarify the maternal effects of GEN on the development and metabolism of chick embryos. GEN treatment at 40 mg/kg increased embryonic length, weight, and liver index, as well as the width of the proliferative zone in the tibial growth plate of chick embryos. Gene ontology (GO) cluster analysis of the hepatic transcriptome showed that GEN treatment promoted embryonic development and cell proliferation...
March 8, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Rob J W Arts, Leo A B Joosten, Mihai G Netea
During induction of trained immunity, monocytes and macrophages undergo a functional and transcriptional reprogramming toward increased activation. Important rewiring of cellular metabolism of the myeloid cells takes place during induction of trained immunity, including a shift toward glycolysis induced through the mTOR pathway, as well as glutaminolysis and cholesterol synthesis. Subsequently, this leads to modulation of the function of epigenetic enzymes, resulting in important changes in chromatin architecture that enables increased gene transcription...
2018: Frontiers in Immunology
Lotte Kors, Elena Rampanelli, Geurt Stokman, Loes Butter, Ntsiki M Held, Nike Claessen, Per W B Larsen, Joanne Verheij, Coert J Zuurbier, Gerhard Liebisch, Gerd Schmitz, Stephen E Girardin, Sandrine Florquin, Riekelt H Houtkooper, Jaklien C Leemans
NOD-like receptor (NLR)X1 (NLRX1) is an ubiquitously expressed inflammasome-independent NLR that is uniquely localized in mitochondria with as yet unknown effects on metabolic diseases. Here, we report that NLRX1 is essential in regulating cellular metabolism in non-immune parenchymal hepatocytes by decreasing mitochondrial fatty acid-dependent oxidative phosphorylation (OXPHOS) and promoting glycolysis. NLRX1 loss in mice has a profound impact on the prevention of diet-induced metabolic syndrome parameters, non-alcoholic fatty liver disease (NAFLD) progression, and renal dysfunction...
March 4, 2018: Biochimica et Biophysica Acta
Alexey Moskalev, Mikhail Shaposhnikov, Nadezhda Zemskaya, Alexey Belyi, Eugenia Dobrovolskaya, Anna Patova, Zulfiya Guvatova, Elena Lukyanova, Anastasiya Snezhkina, Anna Kudryavtseva
BACKGROUND: We have previously showed that the carotenoid fucoxanthin can increase the lifespan in Drosophila melanogaster and Caenorhabditis elegans. However, the molecular mechanisms of the geroprotective effect of fucoxanthin have not been studied so far. RESULTS: Here, we studied the effects of fucoxanthin on the Drosophila aging process at the molecular and the whole organism levels. At the organismal level, fucoxanthin increased the median lifespan and had a positive effect on fecundity, fertility, intestinal barrier function, and nighttime sleep...
February 9, 2018: BMC Genomics
Degao Chen, Jing Xie, Roland Fiskesund, Wenqian Dong, Xiaoyu Liang, Jiadi Lv, Xun Jin, Jinyan Liu, Siqi Mo, Tianzhen Zhang, Feiran Cheng, Yabo Zhou, Huafeng Zhang, Ke Tang, Jingwei Ma, Yuying Liu, Bo Huang
Resetting tumor-associated macrophages (TAMs) is a promising strategy to ameliorate the immunosuppressive tumor microenvironment and improve innate and adaptive antitumor immunity. Here we show that chloroquine (CQ), a proven anti-malarial drug, can function as an antitumor immune modulator that switches TAMs from M2 to tumor-killing M1 phenotype. Mechanistically, CQ increases macrophage lysosomal pH, causing Ca2+ release via the lysosomal Ca2+ channel mucolipin-1 (Mcoln1), which induces the activation of p38 and NF-κB, thus polarizing TAMs to M1 phenotype...
February 28, 2018: Nature Communications
Chunxiao Li, Yu Wang, Yan Li, Qing Yu, Xi Jin, Xiao Wang, Anna Jia, Ying Hu, Linian Han, Jian Wang, Hui Yang, Dapeng Yan, Yujing Bi, Guangwei Liu
Macrophages are important innate immune defense system cells in the fight against bacterial and fungal pathogenic infections. They exhibit significant plasticity, particularly with their ability to undergo functional differentiation. Additionally, HIF1α is critically involved in the functional differentiation of macrophages during inflammation. However, the role of macrophage HIF1α in protecting against different pathogenic infections remains unclear. In this study, we investigated and compared the roles of HIF1α in different macrophage functional effects of bacterial and fungal infections in vitro and in vivo...
February 26, 2018: Scientific Reports
Chika Sakai, Hiroyoshi Nishikawa
Tumor cells establish a unique circumstance called tumor microenvironment(TME)suitable for tumor development and progression. One ofthe most important advantages ofTME for tumor cells is immunosuppressive environment such as higher presence ofregulatory T(Treg)cells, which play a central role for establishment and maintenance of immunological selftolerance and homeostasis. CTLA-4 expressed by Treg cells prevents the maturation ofAPCs resulting in suppression ofT -cell activation. Inhibitory cytokines and adenosine produced by Treg cells are also responsible for their suppressive functions...
February 2018: Gan to Kagaku Ryoho. Cancer & Chemotherapy
Hung D Nguyen, Sandeepkumar Kuril, David Bastian, Xue-Zhong Yu
Metabolism, including catabolism and anabolism, is a basic cellular process necessary for cell survival. T lymphocytes have a distinct metabolism that can determine both fate and function. T-cell activation depends on glycolysis to obtain materials and energy for proliferation and effector function. Importantly, T cells utilize different metabolic processes under different conditions and diseases. Allogeneic hematopoietic cell transplantation (allo-HCT) is a classic immunotherapy for hematological malignancies; however, the development of graft-versus-host disease (GVHD) is a major factor limiting the success of allo-HCT...
2018: Frontiers in Immunology
Jiabi Zhang, Juan Shan, Xuelu Chen, Shengfu Li, Dan Long, Youping Li
A T helper 17 (Th17) cell/regulatory T (Treg) cell imbalance is involved in many immune disorders and diseases. Celastrol, a Chinese herbal compound that has anti-inflammatory and immunosuppressive properties, has been indicated to suppress T cell proliferation and Th17 cell induction, while facilitating Forkhead box P3 (Foxp3) expression and Treg cell generation. In this study, we explored the impact and mechanism of celastrol on Th17 cell/induced Treg (iTreg) cell induction. CD4+ CD25- T cells were purified, stimulated with anti-CD3 and anti-CD28 antibodies, and polarized in vitro to generate Th17 or iTreg cells in the presence or absence of celastrol...
February 21, 2018: Biochemical and Biophysical Research Communications
Xiao Zhu, Yixuan Tu, Hainan Chen, Ampadu O Jackson, Vaibhav Patel, Kai Yin
BACKGROUND: The accumulation and pro-inflammatory polarization of immune cells, mainly macrophages, in adipose tissue (AT) are considered crucial factors for obesity-induced chronic inflammatory diseases. SCOPE OF REVIEW: In this review, we highlighted the role of adipose tissue macrophage (ATM) polarization on AT function in the obese state and the effect of the micro-environment and intracellular metabolism on the dynamic switch of ATMs into their pro-inflammatory or anti-inflammatory phenotypes, which may have distinct influences on obesity-related chronic inflammatory diseases...
February 23, 2018: Diabetes/metabolism Research and Reviews
Ru-Tao Liu, Min Zhang, Chun-Lin Yang, Peng Zhang, Na Zhang, Tong Du, Meng-Ru Ge, Long-Tao Yue, Xiao-Li Li, Heng Li, Rui-Sheng Duan
BACKGROUND: With the recognition of the key roles of cellular metabolism in immunity, targeting metabolic pathway becomes a new strategy for autoimmune disease treatment. Guillain-Barré syndrome (GBS) is an acute immune-mediated inflammatory demyelinating disease of the peripheral nervous system, characterized by inflammatory cell infiltration. These inflammatory cells, including activated macrophages, Th1 cells, and Th17 cells, generally undergo metabolic reprogramming and rely mainly on glycolysis to exert functions...
February 21, 2018: Journal of Neuroinflammation
Qian Li, Dulei Li, Xian Zhang, Qingqing Wan, Wen Zhang, Mingke Zheng, Le Zou, Chris Elly, Jee H Lee, Yun-Cai Liu
Group 2 innate lymphoid cells (ILC2s) are a specialized subset of lymphoid effector cells that are critically involved in allergic responses; however, the mechanisms of their regulation remain unclear. We report that conditional deletion of the E3 ubiquitin ligase VHL in innate lymphoid progenitors minimally affected early-stage bone marrow ILC2s but caused a selective and intrinsic decrease in mature ILC2 numbers in peripheral non-lymphoid tissues, resulting in reduced type 2 immune responses. VHL deficiency caused the accumulation of hypoxia-inducible factor 1α (HIF1α) and attenuated interleukin-33 (IL-33) receptor ST2 expression, which was rectified by HIF1α ablation or inhibition...
February 6, 2018: Immunity
Khalid W Kalim, Jun-Qi Yang, Yuan Li, Yan Meng, Yi Zheng, Fukun Guo
A balance between Th17 cells and regulatory T cells (Tregs) is important for host immunity and immune tolerance. The underlying molecular mechanisms remain poorly understood. Here we have identified Cdc42 as a central regulator of Th17/Treg balance. Deletion of Cdc42 in T cells enhanced Th17 differentiation but diminished induced Treg differentiation and suppressive function. Treg-specific deletion of Cdc42 decreased natural Tregs but increased effector T cells including Th17 cells. Notably, Cdc42-deficient Th17 cells became pathogenic associated with enhanced glycolysis and Cdc42-deficient Tregs became unstable associated with weakened glycolytic signaling...
February 12, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Sundary Sormendi, Ben Wielockx
Low oxygen tension or hypoxia is a determining factor in the course of many different processes in animals, including when tissue expansion and cellular metabolism result in high oxygen demands that exceed its supply. This is mainly happening when cells actively proliferate and the proliferating mass becomes distant from the blood vessels, such as in growing tumors. Metabolic alterations in response to hypoxia can be triggered in a direct manner, such as the switch from oxidative phosphorylation to glycolysis or inhibition of fatty acid desaturation...
2018: Frontiers in Immunology
Akinori Nukui, Yoshiaki Yanai, Toyonori Tsuzuki, Hideyuki Abe, Kyoko Arai, Ken-Ichiro Yoshida, Takao Kamai
Renal cell carcinoma (RCC) is an immunogenic tumor that shows a metabolic shift to aerobic glycolysis. The immune system can have opposing host-protective and tumor-promoting effects, and aerobic glycolysis suppresses antitumor immunity. In addition to immunostimulatory effect, increasing numbers of studies have revealed that interferon (IFN) is also involved in promoting immunosuppression. Since various single nucleotide polymorphisms (SNPs) can influence the outcome of anticancer therapy, we investigated SNPs for IFN-lambda3, a new member of IFN family, in 53 patients with metastatic RCC who underwent cytoreductive nephrectomy...
January 9, 2018: Oncotarget
Thibaut Girardot, Thomas Rimmelé, Guillaume Monneret, Julien Textoris, Fabienne Venet
BACKGROUND: Sepsis-associated hyperlactatemia is a widely used biomarker, associated with initial severity and poor outcomes. This increased circulating lactate concentration has been proposed to result in part from a mismatch between oxygen delivery and demand in organs. However, other mechanisms may participate. In particular, a metabolic reprogramming similar to the Warburg effect initially described in cancer cells could lead to increased lactate production by immune cells such as T lymphocytes after sepsis...
February 5, 2018: Intensive Care Medicine Experimental
Koji Nagaoka, Akihiro Hosoi, Tamaki Iino, Yasuyuki Morishita, Hirokazu Matsushita, Kazuhiro Kakimi
The success of immune checkpoint blockade has unequivocally demonstrated that anti-tumor immunity plays a pivotal role in cancer therapy. Because endogenous tumor-specific T-cell responsiveness is essential for the success of checkpoint blockade, combination therapy with cancer vaccination may facilitate tumor rejection. To select the best vaccine strategy to combine with checkpoint blockade, we compared dendritic cell-based vaccines (DC-V) with peptide vaccines for induction of anti-tumor immunity that could overcome tumor-induced immunosuppression...
2018: Oncoimmunology
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