title: The effect of hyperglycaemia on in vitro cytokine production and macrophage infection with Mycobacterium tuberculosis.
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.
authors: Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands; Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors: Ekta
authors: E
authors: Lachmandas
authors: Department of Infectious Diseases, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Frank
authors: F
authors: Vrieling
authors: Department of Infectious Diseases, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Louis G
authors: LG
authors: Wilson
authors: Department of Infectious Diseases, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Simone A
authors: SA
authors: Joosten
authors: Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands; Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors: Mihai G
authors: MG
authors: Netea
authors: Department of Infectious Diseases, Leiden University Medical Centre, Leiden, The Netherlands.
authors: Tom H
authors: TH
authors: Ottenhoff
authors: Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands; Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors: Reinout
authors: R
authors: van Crevel
mesh_terms: D002176:Candida albicans / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology; D003924:Diabetes Mellitus, Type 2 / Q000276:immunology / Q000382:microbiology; D006801:Humans; D006943:Hyperglycemia / Q000276:immunology* / Q000382:microbiology; D007371:Interferon-gamma / Q000276:immunology*; D007378:Interleukins / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000382:microbiology; D008070:Lipopolysaccharides / Q000276:immunology; D008264:Macrophages / Q000276:immunology* / Q000382:microbiology; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology*
chemical_list: D007378:Interleukins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma