Bacillus Calmette–Guérin (BCG) vaccination induces memory characteristics in innate immune cells and their progenitors, a process called mediated by epigenetic and metabolic reprogramming. Cholesterol synthesis plays an amplifying role in trained immunity through mevalonate release. Nitrogen-containing bisphosphonates (N-BPs), such as alendronate, can inhibit cholesterol synthesis. We explored their effects on trained immunity induced by BCG in a placebo-controlled clinical study (NL74082.091.20) in young, healthy individuals. Participants receiving single-dose oral alendronate on the day of BCG vaccination had more neutrophils and plasma cells one month after treatment. Alendronate led to reduced proinflammatory cytokine production by PBMCs stimulated with heterologous bacterial and viral stimuli one month later. Furthermore, the addition of alendronate transcriptionally suppressed multiple immune response pathways in PBMCs upon stimulation. Our findings indicate that N-BPs modulate the long-lasting effects of BCG vaccination on the cytokine production capacity of innate immune cells.

中文翻译：

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阿仑膦酸钠调节健康年轻人在接种卡介苗后的细胞因子反应

卡介苗 (BCG) 疫苗接种可诱导先天免疫细胞及其祖细胞的记忆特征，这一过程称为表观遗传和代谢重编程介导的过程。胆固醇合成通过甲羟戊酸释放在训练免疫力中发挥放大作用。含氮双膦酸盐（N-BP），例如阿仑膦酸盐，可以抑制胆固醇合成。我们在一项针对年轻健康个体的安慰剂对照临床研究 (NL74082.091.20) 中探讨了它们对 BCG 诱导的训练免疫力的影响。在卡介苗接种当天接受单剂量口服阿仑膦酸钠的参与者在治疗一个月后出现了更多的中性粒细胞和浆细胞。一个月后，阿仑膦酸钠导致受到异源细菌和病毒刺激的 PBMC 促炎细胞因子的产生减少。此外，添加阿仑膦酸钠可在刺激后转录抑制 PBMC 中的多种免疫反应途径。我们的研究结果表明，N-BP 可以调节 BCG 疫苗接种对先天免疫细胞的细胞因子产生能力的长期影响。