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The Effect of Hyperglycaemia on In Vitro Cytokine Production and Macrophage Infection with Mycobacterium tuberculosis

Type 2 diabetes mellitus is an established risk factor for tuberculosis but the underlying mechanisms are largely unknown. We examined the effects of hyperglycaemia, a hallmark of diabetes, on the cytokine response to and macrophage infection with Mycobacterium tuberculosis. Increasing in vitro gluc...

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Autores principales: Lachmandas, Ekta, Vrieling, Frank, Wilson, Louis G., Joosten, Simone A., Netea, Mihai G., Ottenhoff, Tom H., van Crevel, Reinout
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322041/
https://www.ncbi.nlm.nih.gov/pubmed/25664765
http://dx.doi.org/10.1371/journal.pone.0117941
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author Lachmandas, Ekta
Vrieling, Frank
Wilson, Louis G.
Joosten, Simone A.
Netea, Mihai G.
Ottenhoff, Tom H.
van Crevel, Reinout
author_facet Lachmandas, Ekta
Vrieling, Frank
Wilson, Louis G.
Joosten, Simone A.
Netea, Mihai G.
Ottenhoff, Tom H.
van Crevel, Reinout
author_sort Lachmandas, Ekta
collection PubMed
description Type 2 diabetes mellitus is an established risk factor for tuberculosis but the underlying mechanisms are largely unknown. We examined the effects of hyperglycaemia, a hallmark of diabetes, on the cytokine response to and macrophage infection with Mycobacterium tuberculosis. Increasing in vitro glucose concentrations from 5 to 25 mmol/L had marginal effects on cytokine production following stimulation of peripheral blood mononuclear cells (PBMCs) with M. tuberculosis lysate, LPS or Candida albicans, while 40 mmol/L glucose increased production of TNF-α, IL-1β, IL-6 and IL-10, but not of IFN-γ, IL-17A and IL-22. Macrophage differentiation under hyperglycaemic conditions of 25 mmol/L glucose was also associated with increased cytokine production upon stimulation with M. tuberculosis lysate and LPS but in infection experiments no differences in M. tuberculosis killing or outgrowth was observed. The phagocytic capacity of these hyperglycaemic macrophages also remained unaltered. The fact that only very high glucose concentrations were able to significantly influence cytokine production by macrophages suggests that hyperglycaemia alone cannot fully explain the increased susceptibility of diabetes mellitus patients to tuberculosis.
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spelling pubmed-43220412015-02-18 The Effect of Hyperglycaemia on In Vitro Cytokine Production and Macrophage Infection with Mycobacterium tuberculosis Lachmandas, Ekta Vrieling, Frank Wilson, Louis G. Joosten, Simone A. Netea, Mihai G. Ottenhoff, Tom H. van Crevel, Reinout PLoS One Research Article Type 2 diabetes mellitus is an established risk factor for tuberculosis but the underlying mechanisms are largely unknown. We examined the effects of hyperglycaemia, a hallmark of diabetes, on the cytokine response to and macrophage infection with Mycobacterium tuberculosis. Increasing in vitro glucose concentrations from 5 to 25 mmol/L had marginal effects on cytokine production following stimulation of peripheral blood mononuclear cells (PBMCs) with M. tuberculosis lysate, LPS or Candida albicans, while 40 mmol/L glucose increased production of TNF-α, IL-1β, IL-6 and IL-10, but not of IFN-γ, IL-17A and IL-22. Macrophage differentiation under hyperglycaemic conditions of 25 mmol/L glucose was also associated with increased cytokine production upon stimulation with M. tuberculosis lysate and LPS but in infection experiments no differences in M. tuberculosis killing or outgrowth was observed. The phagocytic capacity of these hyperglycaemic macrophages also remained unaltered. The fact that only very high glucose concentrations were able to significantly influence cytokine production by macrophages suggests that hyperglycaemia alone cannot fully explain the increased susceptibility of diabetes mellitus patients to tuberculosis. Public Library of Science 2015-02-09 /pmc/articles/PMC4322041/ /pubmed/25664765 http://dx.doi.org/10.1371/journal.pone.0117941 Text en © 2015 Lachmandas et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Lachmandas, Ekta
Vrieling, Frank
Wilson, Louis G.
Joosten, Simone A.
Netea, Mihai G.
Ottenhoff, Tom H.
van Crevel, Reinout
The Effect of Hyperglycaemia on In Vitro Cytokine Production and Macrophage Infection with Mycobacterium tuberculosis
title The Effect of Hyperglycaemia on In Vitro Cytokine Production and Macrophage Infection with Mycobacterium tuberculosis
title_full The Effect of Hyperglycaemia on In Vitro Cytokine Production and Macrophage Infection with Mycobacterium tuberculosis
title_fullStr The Effect of Hyperglycaemia on In Vitro Cytokine Production and Macrophage Infection with Mycobacterium tuberculosis
title_full_unstemmed The Effect of Hyperglycaemia on In Vitro Cytokine Production and Macrophage Infection with Mycobacterium tuberculosis
title_short The Effect of Hyperglycaemia on In Vitro Cytokine Production and Macrophage Infection with Mycobacterium tuberculosis
title_sort effect of hyperglycaemia on in vitro cytokine production and macrophage infection with mycobacterium tuberculosis
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4322041/
https://www.ncbi.nlm.nih.gov/pubmed/25664765
http://dx.doi.org/10.1371/journal.pone.0117941
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