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Microbial stimulation of different Toll-like receptor signalling pathways induces diverse metabolic programmes in human monocytes

Published on Mar 1, 2017in Nature microbiology14.30
· DOI :10.1038/nmicrobiol.2016.246
Ekta Lachmandas10
Estimated H-index: 10
,
Lily Boutens7
Estimated H-index: 7
+ 9 AuthorsRinke Stienstra29
Estimated H-index: 29
Cite
Abstract
While stimulation of TLR4 with LPS leads to an increase in glycolysis and a decrease in oxidative phosphorylation, complex microbial stimuli and the TLR2 ligand P3C induce upregulation of both glycolysis and oxidative phosphorylation.
  • References (42)
  • Citations (55)
Cite
References42
Newest
Published on Sep 1, 2016in Nature Reviews Immunology44.02
Luke A. J. O'Neill93
Estimated H-index: 93
,
Rigel J. Kishton14
Estimated H-index: 14
,
Jeffrey C. Rathmell59
Estimated H-index: 59
Immunometabolism is emerging an important area of immunological research, but for many immunologists the complexity of the field can be daunting. Here, the authors provide an overview of six key metabolic pathways that occur in immune cells and explain what is known (and what is still to be uncovered) concerning their effects on immune cell function.
Published on Jul 1, 2016in Cell Metabolism22.41
Vicky Lampropoulou15
Estimated H-index: 15
(WashU: Washington University in St. Louis),
Alexey Sergushichev13
Estimated H-index: 13
(WashU: Washington University in St. Louis)
+ 15 AuthorsTakla Griss9
Estimated H-index: 9
(McGill University)
Summary Remodeling of the tricarboxylic acid (TCA) cycle is a metabolic adaptation accompanying inflammatory macrophage activation. During this process, endogenous metabolites can adopt regulatory roles that govern specific aspects of inflammatory response, as recently shown for succinate, which regulates the pro-inflammatory IL-1β-HIF-1α axis. Itaconate is one of the most highly induced metabolites in activated macrophages, yet its functional significance remains unknown. Here, we show that ita...
Published on Jun 1, 2016in Cell36.22
Michael D. Buck16
Estimated H-index: 16
(MPG: Max Planck Society),
David O'Sullivan11
Estimated H-index: 11
(MPG: Max Planck Society)
+ 16 AuthorsGerritje J.W. van der Windt11
Estimated H-index: 11
Summary Activated effector T (T E ) cells augment anabolic pathways of metabolism, such as aerobic glycolysis, while memory T (T M ) cells engage catabolic pathways, like fatty acid oxidation (FAO). However, signals that drive these differences remain unclear. Mitochondria are metabolic organelles that actively transform their ultrastructure. Therefore, we questioned whether mitochondrial dynamics controls T cell metabolism. We show that T E cells have punctate mitochondria, while T M cells main...
Published on Apr 1, 2016in Nature Immunology23.53
Shih-Chin Cheng24
Estimated H-index: 24
,
Brendon P. Scicluna20
Estimated H-index: 20
+ 17 AuthorsOlaf L. Cremer21
Estimated H-index: 21
The acute phase of sepsis is characterized by a strong inflammatory reaction. At later stages in some patients, immunoparalysis may be encountered, which is associated with a poor outcome. By transcriptional and metabolic profiling of human patients with sepsis, we found that a shift from oxidative phosphorylation to aerobic glycolysis was an important component of initial activation of host defense. Blocking metabolic pathways with metformin diminished cytokine production and increased mortalit...
Published on Sep 1, 2015in Journal of Immunology4.72
Elena Izquierdo4
Estimated H-index: 4
(CSIC: Spanish National Research Council),
Víctor D. Cuevas4
Estimated H-index: 4
(CSIC: Spanish National Research Council)
+ 6 AuthorsMaría M. Escribese13
Estimated H-index: 13
(CSIC: Spanish National Research Council)
Macrophages integrate information from the tissue microenvironment and adjust their effector functions according to the prevalent extracellular stimuli. Therefore, macrophages can acquire a variety of activation (polarization) states, and this functional plasticity allows the adequate initiation, regulation, and resolution of inflammatory responses. Modulation of the glucose metabolism contributes to the macrophage adaptation to the surrounding cytokine milieu, as exemplified by the distinct glu...
Published on Aug 14, 2015in Journal of Biological Chemistry
Beth Kelly7
Estimated H-index: 7
(Trinity College, Dublin),
Gillian M. Tannahill7
Estimated H-index: 7
(Trinity College, Dublin)
+ 1 AuthorsLuke A. J. O'Neill93
Estimated H-index: 93
(Trinity College, Dublin)
Abstract Metformin, a frontline treatment for type II diabetes mellitus, decreases production of the pro-form of the inflammatory cytokine IL-1β in response to LPS in macrophages. We found that it specifically inhibited pro-IL-1β production, having no effect on TNF-α. Furthermore, metformin boosted induction of the anti-inflammatory cytokine IL-10 in response to LPS. We ruled out a role for AMP-activated protein kinase (AMPK) in the effect of metformin because activation of AMPK with A769662 did...
Published on Jul 1, 2015in Nucleic Acids Research11.15
Jianguo Xia30
Estimated H-index: 30
(McGill University),
Igor Sinelnikov11
Estimated H-index: 11
(U of A: University of Alberta)
+ 1 AuthorsDavid S. Wishart82
Estimated H-index: 82
(National Institute for Nanotechnology)
MetaboAnalyst (www.metaboanalyst.ca) is a web server designed to permit comprehensive metabolomic data analysis, visualization and interpretation. It supports a wide range of complex statistical calculations and high quality graphical rendering functions that require significant computational resources. First introduced in 2009, MetaboAnalyst has experienced more than a 50X growth in user traffic (>50 000 jobs processed each month). In order to keep up with the rapidly increasing computational d...
Published on Jul 1, 2015in Cell Research17.85
Beth Kelly7
Estimated H-index: 7
,
Luke A. J. O'Neill93
Estimated H-index: 93
Activation of macrophages and dendritic cells (DCs) by pro-inflammatory stimuli causes them to undergo a metabolic switch towards glycolysis and away from oxidative phosphorylation (OXPHOS), similar to the Warburg effect in tumors. However, it is only recently that the mechanisms responsible for this metabolic reprogramming have been elucidated in more detail. The transcription factor hypoxia-inducible factor-1α (HIF-1α) plays an important role under conditions of both hypoxia and normoxia. The ...
Published on Mar 1, 2015in Immunity21.52
Abhishek K. Jha18
Estimated H-index: 18
(Agios Pharmaceuticals),
Stanley Ching-Cheng Huang20
Estimated H-index: 20
(WashU: Washington University in St. Louis)
+ 10 AuthorsBart Everts25
Estimated H-index: 25
(WashU: Washington University in St. Louis)
Summary Macrophage polarization involves a coordinated metabolic and transcriptional rewiring that is only partially understood. By using an integrated high-throughput transcriptional-metabolic profiling and analysis pipeline, we characterized systemic changes during murine macrophage M1 and M2 polarization. M2 polarization was found to activate glutamine catabolism and UDP-GlcNAc-associated modules. Correspondingly, glutamine deprivation or inhibition of N-glycosylation decreased M2 polarizatio...
Published on Jan 2, 2015in Journal of Biological Chemistry
Zheng Tan7
Estimated H-index: 7
(UAB: University of Alabama at Birmingham),
Na Xie15
Estimated H-index: 15
(UAB: University of Alabama at Birmingham)
+ 4 AuthorsGang Liu26
Estimated H-index: 26
(UAB: University of Alabama at Birmingham)
Abstract There has been fast growing evidence showing that glycolysis plays a critical role in the activation of immune cells. Enhanced glycolysis leads to increased formation of intracellular lactate that is exported to the extracellular environment by monocarboxylate transporter 4 (MCT4). Although the biological activities of extracellular lactate have been well studied, it is less understood how the lactate export is regulated or whether lactate export affects glycolysis during inflammatory a...
Cited By55
Newest
Published on Jan 26, 2019in Immunity & Ageing4.25
Brandt D. Pence17
Estimated H-index: 17
(U of M: University of Memphis),
Johnathan R. Yarbro2
Estimated H-index: 2
Background Inflammaging is a condition of chronic low-grade inflammation due to the aging process and is associated with a variety of chronic diseases. Monocytes are innate immune cells which contribute to inflammation and are dysregulated during aging, demonstrated reduced phagocytosis, increased inflammation, and alterations in subset proportions. Metabolism is known to determine immune cell function, with quiescent and anti-inflammatory cells primarily relying on fatty acid oxidation, while a...
Published on 2019in Respiratory Research3.83
Amit Agarwal , Smita Kadam + 6 AuthorsSundeep Salvi26
Estimated H-index: 26
Background Metabolic adaptation in immune cells is necessary to modulate immune cell function as it is intricately coupled with intracellular metabolism. We aimed to characterize the metabolic state of human peripheral blood mononuclear cells (PBMCs) after long-term exposure to tobacco smoke in smokers with preserved lung function and COPD subjects.
Published on Oct 1, 2019in Current Opinion in Immunology7.67
Pedro Escoll8
Estimated H-index: 8
(Pasteur Institute),
Carmen Buchrieser54
Estimated H-index: 54
(Pasteur Institute)
The limited metabolic resources of a cell represent an intriguing ‘conflict of interest’ during host–pathogen interactions, as the battle for nutrients might determine the outcome of an infection. To adapt their metabolic needs, innate immune cells such as monocytes, macrophages or dendritic cells reprogram their metabolism upon activation by microbial compounds. In turn, infection by intracellular bacteria provokes metabolic alterations of the host cell that benefit the pathogen. Here, we discu...
Published on Oct 1, 2019in Mechanisms of Ageing and Development3.60
Johnathan R. Yarbro2
Estimated H-index: 2
(U of M: University of Memphis),
Brandt D. Pence17
Estimated H-index: 17
(U of M: University of Memphis)
ABSTRACT Inflammaging is the chronic low-grade inflammation that occurs with age that contributes to the pathology of age-related diseases. Monocytes are innate immune cells that become dysregulated with age and which can contribute to inflammaging. Metabolism plays a key role in determining immune cell functions, with anti-inflammatory cells primarily relying on fatty acid oxidation and pro-inflammatory cells primarily relying on glycolysis. It was recently shown that lipopolysaccharide (LPS)-s...
Published on Sep 11, 2019in Journal of Leukocyte Biology4.01
Phyu M. Thwe2
Estimated H-index: 2
(UVM: University of Vermont),
Daniel Fritz1
Estimated H-index: 1
(UVM: University of Vermont)
+ 12 AuthorsLaura R. Hoyt4
Estimated H-index: 4
(UVM: University of Vermont)
Published on 2019in Frontiers in Immunology4.72
Man Ks Lee , Annas Al-Sharea5
Estimated H-index: 5
+ 7 AuthorsDarren C. Henstridge23
Estimated H-index: 23
Monocytes in humans consist of 3 subsets; CD14+CD16- (classical), CD14+CD16+ (intermediate) and CD14dimCD16+ (non-classical), which exhibit distinct and heterogeneous responses to activation. During acute inflammation CD14+CD16- monocytes are significantly elevated and migrate to the sites of injury via the adhesion cascade. The field of immunometabolism has begun to elucidate the importance of the engagement of specific metabolic pathways in immune cell function. Yet, little is known about mono...
Published on Apr 24, 2019in The Journal of Infectious Diseases5.04
Martin Jaeger17
Estimated H-index: 17
(Radboud University Nijmegen),
Vasiliki Matzaraki (Radboud University Nijmegen)+ 15 AuthorsSanne P. Smeekens24
Estimated H-index: 24
(Radboud University Nijmegen)
Published on May 3, 2019in Cardiovascular Research7.01
Julia van Tuijl1
Estimated H-index: 1
(Radboud University Nijmegen),
Leo A. B. Joosten81
Estimated H-index: 81
(Radboud University Nijmegen)
+ 2 AuthorsNiels P. Riksen21
Estimated H-index: 21
(Radboud University Nijmegen)
Published on Jul 1, 2019in Molecular Immunology3.06
Gustavo Aldapa-Vega1
Estimated H-index: 1
(IPN: Instituto Politécnico Nacional),
Víctor Manuel Vargas-Hernández8
Estimated H-index: 8
+ 10 AuthorsIsibasi Armando23
Estimated H-index: 23
(Mexican Social Security Institute)
Abstract Salmonella enterica serovar Typhimurium ( S. Typhimurium) changes the structure of its lipopolysaccharide (LPS) in response to the environment. The two main LPS variants found in S. Typhimurium correspond to LPS with a hepta-acylated lipid A (LPS 430) and LPS with modified phosphate groups on its lipid A (LPS 435). We have previously shown that these modified LPS have a lower capacity than wild type (WT) LPS to induce the production of pro-inflammatory cytokines in mice. Nevertheless, i...
Published on Jun 21, 2019in EMBO Reports8.38
Ana Traven21
Estimated H-index: 21
(Monash University, Clayton campus),
Thomas Naderer21
Estimated H-index: 21
(Monash University, Clayton campus)