Lachmandas Ekta, Vrieling Frank, Wilson Louis G, Joosten Simone A, Netea Mihai G, Ottenhoff Tom H, van Crevel Reinout
Department of Internal Medicine, Radboud University Medical Centre, Nijmegen, The Netherlands; Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands.
Department of Infectious Diseases, Leiden University Medical Centre, Leiden, The Netherlands.
PLoS One. 2015 Feb 9;10(2):e0117941. doi: 10.1371/journal.pone.0117941. eCollection 2015.
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.
2型糖尿病是结核病的一个既定危险因素，但其潜在机制大多未知。我们研究了高血糖（糖尿病的一个标志）对结核分枝杆菌细胞因子反应和巨噬细胞感染的影响。将体外葡萄糖浓度从5 mmol/L提高到25 mmol/L，在用结核分枝杆菌裂解物、脂多糖或白色念珠菌刺激外周血单核细胞（PBMC）后，对细胞因子产生的影响很小，而40 mmol/L葡萄糖增加了TNF-α、IL-1β、IL-6和IL-10的产生，但未增加IFN-γ、IL-17A和IL-22的产生。在25 mmol/L葡萄糖的高血糖条件下巨噬细胞分化，在用结核分枝杆菌裂解物和脂多糖刺激后也与细胞因子产生增加有关，但在感染实验中，未观察到结核分枝杆菌杀伤或生长的差异。这些高血糖巨噬细胞的吞噬能力也保持不变。只有非常高的葡萄糖浓度才能显著影响巨噬细胞产生细胞因子，这一事实表明，仅高血糖不能完全解释糖尿病患者对结核病易感性增加的原因。
