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Glycolytic activity in human immune cells: inter-individual variation and functional implications during health and diabetes

An increase in glucose uptake driving aerobic glycolysis is a robust hallmark of immune cell activation. The glycolytic response supports functional alterations of the innate immune cells including the production and release of cytokines. Large inter-individual differences in the magnitude of this c...

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Autores principales: Vrieling, Frank, van Dierendonck, Xanthe A. M. H., Jaeger, Martin, Janssen, Anna W. M., Hijmans, Anneke, Netea, Mihai G., Tack, Cees J., Stienstra, Rinke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9624385/
https://www.ncbi.nlm.nih.gov/pubmed/36337734
http://dx.doi.org/10.1097/IN9.0000000000000008
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author Vrieling, Frank
van Dierendonck, Xanthe A. M. H.
Jaeger, Martin
Janssen, Anna W. M.
Hijmans, Anneke
Netea, Mihai G.
Tack, Cees J.
Stienstra, Rinke
author_facet Vrieling, Frank
van Dierendonck, Xanthe A. M. H.
Jaeger, Martin
Janssen, Anna W. M.
Hijmans, Anneke
Netea, Mihai G.
Tack, Cees J.
Stienstra, Rinke
author_sort Vrieling, Frank
collection PubMed
description An increase in glucose uptake driving aerobic glycolysis is a robust hallmark of immune cell activation. The glycolytic response supports functional alterations of the innate immune cells including the production and release of cytokines. Large inter-individual differences in the magnitude of this cytokine response are known to exist. In addition, the presence of disease is known to impact on immune cell function. Whether variation in metabolic responses of immune cells exist between individuals during health or disease is currently unknown. Here, we explore inter-individual differences in the glycolytic rate of immune cells using lactate production as readout upon activation using a variety of different stimuli. Glycolytic responses are subsequently associated to functional immune cell responses in healthy humans. In addition, we determined the glycolytic rate of immune cells and its association with immune function using patients diagnosed with diabetes mellitus. Based on the relative increase in lactate production after activation, distinct clusters of low, intermediate, and high responders could be identified, illustrating the existence of variation in glycolytic responses in healthy subjects. Interestingly, the production of cytokines mirrored these high-, intermediate-, and low-lactate patterns after pathogenic stimulation. In patients with diabetes mellitus, a reduced correlation was found between lactate and cytokine production, specifically for IL-6. Furthermore, based on the relative increase in lactate production, variability in the glycolytic response was reduced compared to healthy subjects. In conclusion, our results show a specific association between the glycolytic rate and function in human immune cells after stimulation with different pathogens. In addition to demonstrating the existence of glycolytic variability and specificity depending on the type of stimulus, the association between glycolysis and function in innate immune cells is altered during the presence of diabetes.
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spelling pubmed-96243852022-11-04 Glycolytic activity in human immune cells: inter-individual variation and functional implications during health and diabetes Vrieling, Frank van Dierendonck, Xanthe A. M. H. Jaeger, Martin Janssen, Anna W. M. Hijmans, Anneke Netea, Mihai G. Tack, Cees J. Stienstra, Rinke Immunometabolism (Cobham) Article An increase in glucose uptake driving aerobic glycolysis is a robust hallmark of immune cell activation. The glycolytic response supports functional alterations of the innate immune cells including the production and release of cytokines. Large inter-individual differences in the magnitude of this cytokine response are known to exist. In addition, the presence of disease is known to impact on immune cell function. Whether variation in metabolic responses of immune cells exist between individuals during health or disease is currently unknown. Here, we explore inter-individual differences in the glycolytic rate of immune cells using lactate production as readout upon activation using a variety of different stimuli. Glycolytic responses are subsequently associated to functional immune cell responses in healthy humans. In addition, we determined the glycolytic rate of immune cells and its association with immune function using patients diagnosed with diabetes mellitus. Based on the relative increase in lactate production after activation, distinct clusters of low, intermediate, and high responders could be identified, illustrating the existence of variation in glycolytic responses in healthy subjects. Interestingly, the production of cytokines mirrored these high-, intermediate-, and low-lactate patterns after pathogenic stimulation. In patients with diabetes mellitus, a reduced correlation was found between lactate and cytokine production, specifically for IL-6. Furthermore, based on the relative increase in lactate production, variability in the glycolytic response was reduced compared to healthy subjects. In conclusion, our results show a specific association between the glycolytic rate and function in human immune cells after stimulation with different pathogens. In addition to demonstrating the existence of glycolytic variability and specificity depending on the type of stimulus, the association between glycolysis and function in innate immune cells is altered during the presence of diabetes. Lippincott Williams & Wilkins 2022-11-01 /pmc/articles/PMC9624385/ /pubmed/36337734 http://dx.doi.org/10.1097/IN9.0000000000000008 Text en Copyright © 2022 The Author(s), Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by/4.0/This paper is published under Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Vrieling, Frank
van Dierendonck, Xanthe A. M. H.
Jaeger, Martin
Janssen, Anna W. M.
Hijmans, Anneke
Netea, Mihai G.
Tack, Cees J.
Stienstra, Rinke
Glycolytic activity in human immune cells: inter-individual variation and functional implications during health and diabetes
title Glycolytic activity in human immune cells: inter-individual variation and functional implications during health and diabetes
title_full Glycolytic activity in human immune cells: inter-individual variation and functional implications during health and diabetes
title_fullStr Glycolytic activity in human immune cells: inter-individual variation and functional implications during health and diabetes
title_full_unstemmed Glycolytic activity in human immune cells: inter-individual variation and functional implications during health and diabetes
title_short Glycolytic activity in human immune cells: inter-individual variation and functional implications during health and diabetes
title_sort glycolytic activity in human immune cells: inter-individual variation and functional implications during health and diabetes
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9624385/
https://www.ncbi.nlm.nih.gov/pubmed/36337734
http://dx.doi.org/10.1097/IN9.0000000000000008
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