Metabolic Insight of Neutrophils in Health and Disease

Kumar, Sachin; Dikshit, Madhu

doi:10.3389/fimmu.2019.02099

Cited by 171 publications

(170 citation statements)

References 162 publications

(277 reference statements)

Supporting

Mentioning

169

Contrasting

Order By: Relevance

“…where this module is also most enriched in progenitor populations. Interestingly, mTMS singlecell RNA-seq data also demonstrate that this module is enriched in neutrophils, in accord with described high glycolytic rate in these cells 24 .…”

Section: Subnetwork Associated With Early Developmental Stagessupporting

confidence: 71%

Open Source ImmGen: network perspective on metabolic diversity among mononuclear phagocytes

Gainullina

Huang

Todorov

et al. 2020

Preprint

View full text Add to dashboard Cite

We dissect metabolic variability of mononuclear phagocyte (MNP) subpopulations across different tissues through integrative analysis of three large scale datasets. Specifically, we introduce ImmGen MNP Open Source dataset that profiled 337 samples and extended previous ImmGen effort which included 202 samples of mononuclear phagocytes and their progenitors. Next, we analysed Tabula Muris Senis dataset to extract data for 51,364 myeloid cells from 18 tissues. Taken together, a compendium of data assembled in this work covers phagocytic populations found across 38 different tissues. To analyse common metabolic features, we developed novel network-based computational approach for unbiased identification of key metabolic subnetworks based on cellular transcriptional profiles in large-scale datasets. Using ImmGen MNP Open Source dataset as baseline, we define 9 metabolic subnetworks that encapsulate the metabolic differences within mononuclear phagocytes, and demonstrate that these features are robustly found across all three datasets, including lipid metabolism, cholesterol biosynthesis, glycolysis, and a set of fatty acid related metabolic pathways, as well as nucleotide and folate metabolism. We systematically define major features specific to macrophage and dendritic cell subpopulations. Among other things, we find that cholesterol synthesis appears particularly active within the migratory dendritic cells. We demonstrate that interference with this pathway through statins administration diminishes migratory capacity of the dendritic cells in vivo. This result demonstrates the power of our approach and highlights importance of metabolic diversity among mononuclear phagocytes.

show abstract

Section: Subnetwork Associated With Early Developmental Stagessupporting

confidence: 71%

Open Source ImmGen: network perspective on metabolic diversity among mononuclear phagocytes

Gainullina

Huang

Todorov

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…These processes consume enormous amount of oxygen, ATP and NADPH and thus leads to significant metabolic changes (Kapoor et al, 2013). Critical metabolic changes and distinct phenotypes have been identified that are required for neutrophil differentiation and functions (Kumar and Dikshit, 2019;(Viola et al, 2019).…”

Section: Other Immune Cells Metabolismmentioning

confidence: 99%

Metabolic Reprogramming—A New Era How to Prevent and Treat Graft Versus Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation Has Begun

Kumari

Palaniyandi

2020

Front. Pharmacol.

View full text Add to dashboard Cite

Allogeneic hematopoietic stem cell transplantation (HSCT) is the solitary therapeutic therapy for many types of hematological cancers. The benefits of this procedure are challenged by graft vs. host disease (GVHD), causing significant morbidity and mortality. Recent advances in the metabolomics field have revolutionized our understanding of complex human diseases, clinical diagnostics and allow to trace the de novo biosynthesis of metabolites. There is growing evidence for metabolomics playing a role in different aspects of GVHD, and therefore metabolomic reprogramming presents a novel tool for this disease. Pre-transplant cytokine profiles and metabolic status of allogeneic transplant recipients is shown to be linked with a threat of acute GVHD. Immune reactions underlying the pathophysiology of GVHD involve higher proliferation and migration of immune cells to the target site, requiring shifts in energy supply and demand. Metabolic changes and reduced availability of oxygen result in tissue and cellular hypoxia which is extensive enough to trigger transcriptional and translational changes. T cells, major players in acute GVHD pathophysiology, show increased glucose uptake and glycolytic activity. Effector T (Teff) cells activated during nutrient limiting conditions in vitro or multiplying during GVHD in vivo, depend more on oxidative phosphorylation (OXPHOS) and fatty acid oxidation (FAO). Dyslipidemia, such as the increase of medium and long chain fatty and polyunsaturated acids in plasma of GVHD patients, has been observed. Sphingolipids associate with inflammatory conditions and cancer. Chronic GVHD (cGVHD) patients show reduced branched-chain amino acids (BCAAs) and increased sulfur-containing metabolites post HSCT. Microbiota-derived metabolites such as aryl hydrocarbon receptor (AhR) ligands, bile acids, plasmalogens and short chain fatty acids vary significantly and affect allogeneic immune responses during acute GVHD. Considering the multitude of possibilities, how altered metabolomics are involved in GVHD biology, multi-timepoints related and multivariable biomarker panels for prognosticating and understanding GVHD are needed. In this review, we will discuss the recent work addressing metabolomics reprogramming to control GVHD in detail.

show abstract

“…For example, ISG15 is an interferon-stimulated, ubiquitin-like protein which regulates mitochondrial homeostasis and targets various proteins involved in catabolic autophagy metabolism in the mitochondria (mitophagy) during infection [103,104]. Moreover, mitochondrial changes in immunometabolism (glycolysis, the tricarboxylic acid (TCA) cycle, the pentose phosphate pathway, fatty acid oxidation, fatty acid synthesis and amino acid metabolism) strongly contribute in (re)shaping immunity and production of neutrophil extracellular traps (NETs) [105][106][107][108].…”

Section: Discussionmentioning

confidence: 99%

Standardized Echinacea purpurea extract primes an IFN specific innate immune monocyte response via JAK1-STAT1 dependent gene expression and epigenetic control of endogenous retroviral sequences

Declerck¹,

Pérez-Novo²,

Grielens³

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Herbal remedies of Echinacea purpurea tinctures are widely used today to reduce common cold respiratory tract infections.Methods: A system biology approach involving genomewide transcriptome, epigenome and kinome activity profiles was applied to characterize the immunomodulatory effects of a standardized Echinacea purpurea extract Echinaforce® in THP1 monocytes.Results: Gene expression and DNA methylation analysis revealed activation of innate immunity related antiviral signaling networks, involving IFN, chemotaxis and immunometabolic pathways. Furthermore, phosphopeptide based kinome activity profiling and pharmacological inhibitor experiments with filgotinib confirm a key role for Janus Kinase (JAK)-1 dependent gene expression changes in innate immune signaling. Finally, Echinaforce® treatment induces DNA hypermethylation at intergenic CpG, long/short interspersed nuclear DNA repeat elements (LINE, SINE) or long termininal DNA repeats (LTR). This changes transcription of flanking endogenous retroviral sequences (HERVs), involved in an evolutionary conserved (epi)genomic protective response against viral infections.Conclusions: Altogether, our results suggest that Echinaforce® phytochemicals strengthen antiviral innate immunity by JAK1 responsive gene expression and epigenetic regulation of HERVs in monocytes, which supports its prophylactic use against common cold corona viruses (CoV), Severe Acute Respiratory Syndrome (SARS)-CoV, and new occurring strains such as SARS-CoV-2.

show abstract

Metabolic Insight of Neutrophils in Health and Disease

Cited by 171 publications

References 162 publications

Open Source ImmGen: network perspective on metabolic diversity among mononuclear phagocytes

Open Source ImmGen: network perspective on metabolic diversity among mononuclear phagocytes

Metabolic Reprogramming—A New Era How to Prevent and Treat Graft Versus Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation Has Begun

Standardized Echinacea purpurea extract primes an IFN specific innate immune monocyte response via JAK1-STAT1 dependent gene expression and epigenetic control of endogenous retroviral sequences

Contact Info

Product

Resources

About