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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Main Authors: Ekta Lachmandas, Frank Vrieling, Louis G Wilson, Simone A Joosten, Mihai G Netea, Tom H Ottenhoff, Reinout van Crevel
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2015-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC4322041?pdf=render
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author Ekta Lachmandas
Frank Vrieling
Louis G Wilson
Simone A Joosten
Mihai G Netea
Tom H Ottenhoff
Reinout van Crevel
author_facet Ekta Lachmandas
Frank Vrieling
Louis G Wilson
Simone A Joosten
Mihai G Netea
Tom H Ottenhoff
Reinout van Crevel
author_sort Ekta Lachmandas
collection DOAJ
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 doaj.art-654bd959c93543248bf417ae1315fc7c2022-12-21T22:35:55ZengPublic Library of Science (PLoS)PLoS ONE1932-62032015-01-01102e011794110.1371/journal.pone.0117941The effect of hyperglycaemia on in vitro cytokine production and macrophage infection with Mycobacterium tuberculosis.Ekta LachmandasFrank VrielingLouis G WilsonSimone A JoostenMihai G NeteaTom H OttenhoffReinout van CrevelType 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.http://europepmc.org/articles/PMC4322041?pdf=render
spellingShingle Ekta Lachmandas
Frank Vrieling
Louis G Wilson
Simone A Joosten
Mihai G Netea
Tom H Ottenhoff
Reinout van Crevel
The effect of hyperglycaemia on in vitro cytokine production and macrophage infection with Mycobacterium tuberculosis.
PLoS ONE
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
url http://europepmc.org/articles/PMC4322041?pdf=render
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