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Glucose metabolism is upregulated in the mononuclear cell proteome during sepsis and supports endotoxin-tolerant cell function
Metabolic adaptations shape immune cell function. In the acute response, a metabolic switch towards glycolysis is necessary for mounting a proinflammatory response. During the clinical course of sepsis, both suppression and activation of immune responses take place simultaneously. Leukocytes from se...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9718365/ https://www.ncbi.nlm.nih.gov/pubmed/36466921 http://dx.doi.org/10.3389/fimmu.2022.1051514 |
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author | Ferreira, Bianca Lima Sousa, Mônica Bragança Leite, Giuseppe Gianini Figueirêdo Brunialti, Milena Karina Colo Nishiduka, Erika Sayuri Tashima, Alexandre Keiji van der Poll, Tom Salomão, Reinaldo |
author_facet | Ferreira, Bianca Lima Sousa, Mônica Bragança Leite, Giuseppe Gianini Figueirêdo Brunialti, Milena Karina Colo Nishiduka, Erika Sayuri Tashima, Alexandre Keiji van der Poll, Tom Salomão, Reinaldo |
author_sort | Ferreira, Bianca Lima |
collection | PubMed |
description | Metabolic adaptations shape immune cell function. In the acute response, a metabolic switch towards glycolysis is necessary for mounting a proinflammatory response. During the clinical course of sepsis, both suppression and activation of immune responses take place simultaneously. Leukocytes from septic patients present inhibition of cytokine production while other functions such as phagocytosis and production of reactive oxygen species (ROS) are preserved, similarly to the in vitro endotoxin tolerance model, where a first stimulation with lipopolysaccharide (LPS) affects the response to a second stimulus. Here, we sought to investigate how cellular metabolism is related to the modulation of immune responses in sepsis and endotoxin tolerance. Proteomic analysis in peripheral blood mononuclear cells (PBMCs) from septic patients obtained at intensive care unit admission showed an upregulation of proteins related to glycolysis, the pentose phosphate pathway (PPP), production of ROS and nitric oxide, and downregulation of proteins in the tricarboxylic acid cycle and oxidative phosphorylation compared to healthy volunteers. Using the endotoxin-tolerance model in PBMCs from healthy subjects, we observed increased lactate production in control cells upon LPS stimulation, while endotoxin-tolerant cells presented inhibited tumor necrosis factor-α and lactate production along with preserved phagocytic capacity. Inhibition of glycolysis and PPP led to impairment of phagocytosis and cytokine production both in control and in endotoxin-tolerant cells. These data indicate that glucose metabolism supports leukocyte functions even in a condition of endotoxin tolerance. |
format | Online Article Text |
id | pubmed-9718365 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-97183652022-12-03 Glucose metabolism is upregulated in the mononuclear cell proteome during sepsis and supports endotoxin-tolerant cell function Ferreira, Bianca Lima Sousa, Mônica Bragança Leite, Giuseppe Gianini Figueirêdo Brunialti, Milena Karina Colo Nishiduka, Erika Sayuri Tashima, Alexandre Keiji van der Poll, Tom Salomão, Reinaldo Front Immunol Immunology Metabolic adaptations shape immune cell function. In the acute response, a metabolic switch towards glycolysis is necessary for mounting a proinflammatory response. During the clinical course of sepsis, both suppression and activation of immune responses take place simultaneously. Leukocytes from septic patients present inhibition of cytokine production while other functions such as phagocytosis and production of reactive oxygen species (ROS) are preserved, similarly to the in vitro endotoxin tolerance model, where a first stimulation with lipopolysaccharide (LPS) affects the response to a second stimulus. Here, we sought to investigate how cellular metabolism is related to the modulation of immune responses in sepsis and endotoxin tolerance. Proteomic analysis in peripheral blood mononuclear cells (PBMCs) from septic patients obtained at intensive care unit admission showed an upregulation of proteins related to glycolysis, the pentose phosphate pathway (PPP), production of ROS and nitric oxide, and downregulation of proteins in the tricarboxylic acid cycle and oxidative phosphorylation compared to healthy volunteers. Using the endotoxin-tolerance model in PBMCs from healthy subjects, we observed increased lactate production in control cells upon LPS stimulation, while endotoxin-tolerant cells presented inhibited tumor necrosis factor-α and lactate production along with preserved phagocytic capacity. Inhibition of glycolysis and PPP led to impairment of phagocytosis and cytokine production both in control and in endotoxin-tolerant cells. These data indicate that glucose metabolism supports leukocyte functions even in a condition of endotoxin tolerance. Frontiers Media S.A. 2022-11-18 /pmc/articles/PMC9718365/ /pubmed/36466921 http://dx.doi.org/10.3389/fimmu.2022.1051514 Text en Copyright © 2022 Ferreira, Sousa, Leite, Brunialti, Nishiduka, Tashima, van der Poll and Salomão https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Immunology Ferreira, Bianca Lima Sousa, Mônica Bragança Leite, Giuseppe Gianini Figueirêdo Brunialti, Milena Karina Colo Nishiduka, Erika Sayuri Tashima, Alexandre Keiji van der Poll, Tom Salomão, Reinaldo Glucose metabolism is upregulated in the mononuclear cell proteome during sepsis and supports endotoxin-tolerant cell function |
title | Glucose metabolism is upregulated in the mononuclear cell proteome during sepsis and supports endotoxin-tolerant cell function |
title_full | Glucose metabolism is upregulated in the mononuclear cell proteome during sepsis and supports endotoxin-tolerant cell function |
title_fullStr | Glucose metabolism is upregulated in the mononuclear cell proteome during sepsis and supports endotoxin-tolerant cell function |
title_full_unstemmed | Glucose metabolism is upregulated in the mononuclear cell proteome during sepsis and supports endotoxin-tolerant cell function |
title_short | Glucose metabolism is upregulated in the mononuclear cell proteome during sepsis and supports endotoxin-tolerant cell function |
title_sort | glucose metabolism is upregulated in the mononuclear cell proteome during sepsis and supports endotoxin-tolerant cell function |
topic | Immunology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9718365/ https://www.ncbi.nlm.nih.gov/pubmed/36466921 http://dx.doi.org/10.3389/fimmu.2022.1051514 |
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