Department of Internal Medicine (463), Radboud Institute for Molecular Life Sciences, Radboud University Medical Centre, Geert Grooteplein zuid 8, 6525 GA, Nijmegen, The Netherlands.
Radboud Centre for Infectious Diseases, Radboud University Medical Centre, Nijmegen, The Netherlands.
Eur J Clin Microbiol Infect Dis. 2018 Feb;37(2):371-380. doi: 10.1007/s10096-017-3145-y. Epub 2017 Nov 30.
Patients with diabetes mellitus have an increased risk of developing tuberculosis. Although the underlying mechanism is unclear, evidence suggests a role for chronic hyperglycaemia. We examined the influence of hyperglycaemia on Mycobacterium tuberculosis-induced cytokine responses in patients with type 1 diabetes mellitus (T1D). Peripheral blood mononuclear cells (PBMCs) from 24 male T1D patients with sub-optimal glucose control [HbA1c > 7.0% (53 mmol/L)] and from 24 age-matched male healthy controls were stimulated with M. tuberculosis lysate. Cytokine analysis, assessment of aerobic glycolysis, receptor recognition and serum cross-over experiments were performed to explore the mechanistic differences. PBMCs from T1D patients produced less bioactive interleukin (IL)-1β in response to M. tuberculosis. IL-6 and interferon (IFN)-γ production trended towards a decrease, whilst other cytokines such as tumour necrosis factor (TNF)-α, IL-17 and IL-1Ra were normal. The decrease in cytokine production was not correlated to HbA1c or plasma glucose levels. Cross-over serum experiments did not alter the cytokine profile of T1D or control patients, arguing for an intrinsic cellular defect. Cellular metabolism and the expression of M. tuberculosis-related pattern recognition receptors (PRRs) such as TLR2, TLR4 and NOD2 did not differ between T1D patients and healthy controls. Compared to matched controls, T1D patients have a reduced capacity to produce pro-inflammatory cytokines in response to M. tuberculosis. The impaired IL-1β production in T1D patients may contribute to the increased susceptibility to tuberculosis. This effect appears not to be related to prevailing glucose levels but to an intrinsic cellular deficit.
糖尿病患者发生结核病的风险增加。尽管其潜在机制尚不清楚，但有证据表明与慢性高血糖有关。我们研究了高血糖对 1 型糖尿病（T1D）患者中结核分枝杆菌诱导的细胞因子反应的影响。来自 24 名血糖控制不佳（HbA1c>7.0%（53mmol/L））的男性 T1D 患者和 24 名年龄匹配的男性健康对照者的外周血单核细胞（PBMC）用结核分枝杆菌裂解物刺激。进行细胞因子分析、有氧糖酵解评估、受体识别和血清交叉实验，以探讨其机制差异。与结核分枝杆菌反应时，T1D 患者产生的生物活性白细胞介素（IL）-1β较少。IL-6 和干扰素（IFN）-γ的产生呈下降趋势，而其他细胞因子如肿瘤坏死因子（TNF）-α、IL-17 和 IL-1Ra 则正常。细胞因子产生的减少与 HbA1c 或血浆葡萄糖水平无关。交叉血清实验未改变 T1D 或对照患者的细胞因子谱，这表明是细胞内在缺陷。细胞代谢和结核分枝杆菌相关模式识别受体（PRR）如 TLR2、TLR4 和 NOD2 的表达在 T1D 患者和健康对照者之间没有差异。与匹配对照者相比，T1D 患者对结核分枝杆菌的反应产生促炎细胞因子的能力降低。T1D 患者中 IL-1β 产生减少可能导致结核病易感性增加。这种效应似乎与当前的血糖水平无关，而是与细胞内在缺陷有关。
