The effect of hyperglycaemia on in vitro cytokine production and macrophage infection with Mycobacterium tuberculosis

PLoS One. 2015 Feb 9;10(2):e0117941. doi: 10.1371/journal.pone.0117941. eCollection 2015.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Candida albicans / immunology
  • Cell Differentiation / immunology
  • Diabetes Mellitus, Type 2 / immunology
  • Diabetes Mellitus, Type 2 / microbiology
  • Humans
  • Hyperglycemia / immunology*
  • Hyperglycemia / microbiology
  • Interferon-gamma / immunology*
  • Interleukins / immunology*
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / microbiology
  • Lipopolysaccharides / immunology
  • Macrophages / immunology*
  • Macrophages / microbiology
  • Middle Aged
  • Mycobacterium tuberculosis / immunology*
  • Tuberculosis / immunology
  • Tuberculosis / microbiology
  • Tumor Necrosis Factor-alpha / immunology*

Substances

  • Interleukins
  • Lipopolysaccharides
  • Tumor Necrosis Factor-alpha
  • Interferon-gamma

Grant support

This study was supported by the TANDEM (Tuberculosis and Diabetes Mellitus) Grant of the EC-FP7 (European Union’s Seventh Framework Programme) under Grant Agreement No. 305279. MGN was supported by an ERC (European Research Council) Starting Grant (ERC#310372). RvC was supported by a Vidi grant of NWO (Nederlandse Organisatie voor Wetenschappelijk Onderzoek)(No. 91710310). SAJ and THO were supported by EC-FP7 EURIPRED INFRASTRUCTURES (European Research Infrastructures for Poverty Related Diseases), contract no. .2012.1 312661, EC-FP7 ADITEC (Advanced Immunization Technologies) Grant agreement no. 280873 and LUMC (Leiden University Medical Center) Profiling area grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.