Department of Medicine, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden; Almazov Federal Heart, Blood and Endocrinology Centre, St. Petersburg, Russia.
J Intern Med. 2014 Jan;275(1):49-58. doi: 10.1111/joim.12127. Epub 2013 Sep 12.
Atherosclerosis is an inflammatory disease of the arterial wall that leads to myocardial infarction and stroke. Regulatory T cells (Tregs) and IL-10 exert significant anti-atherogenic effects in experimental models of atherosclerosis by modulating vascular inflammation. We have previously shown that Mycobacterium bovis BCG killed by extended freeze-drying (EFD BCG) decreases lung and colon inflammation by recruiting IL-10-producing Tregs. Therefore, the aim of this study was to investigate the effect of EFD BCG on the development of atherosclerosis.
We used two strains of atherosclerosis-prone mice: Ldlr(-/-) (four or six EFD BCG injections) and Apoe(-/-) (six injections).
In both models, EFD BCG significantly reduced the size of atherosclerotic lesions, increased IL-10 production and reduced the serum levels of pro-inflammatory cytokines (IL-6, IL-13, KC and tumour necrosis factor-α). Shortly after treatment with EFD BCG, the number of plasmacytoid dendritic cells (pDCs) and Foxp3(+) Tregs in the draining lymph nodes increased. EFD BCG also led to accumulation of Tregs, but not of pDCs in the spleen, and reduced activity of NF-κB and increased activity of PPAR-γ in both the spleen and vascular tissue of treated mice.
EFD BCG has atheroprotective effects through IL-10 production and Treg expansion. These findings support a novel approach to the prevention and treatment of atherosclerosis.
动脉粥样硬化是一种动脉壁的炎症性疾病，可导致心肌梗死和中风。调节性 T 细胞（Tregs）和 IL-10 通过调节血管炎症，在动脉粥样硬化的实验模型中发挥显著的抗动脉粥样硬化作用。我们之前已经表明，经延长冻干（EFD BCG）杀死的牛分枝杆菌（Mycobacterium bovis BCG）通过募集产生 IL-10 的 Tregs 来减少肺和结肠炎症。因此，本研究的目的是研究 EFD BCG 对动脉粥样硬化发展的影响。
我们使用了两种易患动脉粥样硬化的小鼠模型：Ldlr（-/-）（四或六次 EFD BCG 注射）和 Apoe（-/-）（六次注射）。
在这两种模型中，EFD BCG 均显著减小动脉粥样硬化病变的大小，增加 IL-10 产生，并降低促炎细胞因子（IL-6、IL-13、KC 和肿瘤坏死因子-α）的血清水平。在接受 EFD BCG 治疗后不久，引流淋巴结中的浆细胞样树突状细胞（pDCs）和 Foxp3（+）Tregs 的数量增加。EFD BCG 还导致 Tregs 而不是 pDCs 在脾脏中的积累，并降低了治疗小鼠脾脏和血管组织中 NF-κB 的活性，增加了 PPAR-γ 的活性。
EFD BCG 通过产生 IL-10 和 Treg 扩增发挥抗动脉粥样硬化作用。这些发现支持了预防和治疗动脉粥样硬化的新方法。
