卡介苗诱导训练免疫研究进展及其应用

Research progress and application in trained immunity induced by Mycobacterium bovis BCG

摘要:

训练免疫属于先天免疫反应，其特征是先天免疫细胞表观遗传重编程、代谢重编程。通过某些刺激(如疫苗、微生物或其产物)可激发先天免疫细胞，如单核细胞、中性粒细胞和骨髓干细胞的训练免疫，若重新刺激，可增强先天免疫细胞对微生物病原体的免疫反应。牛分枝杆菌(Mycobacterium bovis)卡介苗(Bacillus Calmette-Guérin, BCG)、β-葡聚糖[白色念珠菌(Candida albicans)主要细胞壁成分]等通过激活先天免疫细胞核转录因子-κB (nucleus factor -κB, NF-κB)通路或者树突状细胞相关C型凝集素-1/蛋白激酶B/哺乳动物雷帕霉素靶蛋白/低氧诱导因子-1α (dendritic cell-associated C-type lectin 1/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor 1-alpha, Dectin-1/Akt/mTOR/HIF-1α)信号通路调控细胞代谢重编程和表观遗传重编程，从而诱导训练免疫。先天免疫细胞中训练免疫的发现为新疫苗的研发、免疫缺陷状态的治疗策略及调节自身炎症性疾病提供新的方向。因此，了解BCG诱导训练免疫的细胞学机制，可对未知疾病的预防有重大意义。

关键词:训练免疫;先天免疫细胞;卡介苗

Abstract:

Trained immunity, a functional state of the innate immune response, is characterized by epigenetic reprogramming and metabolic reprogramming of innate immune cells. Stimuli such as vaccines and microorganisms or their products can stimulate the trained immunity of innate immune cells, such as monocytes, neutrophils, and bone marrow stem cells. The re-stimulation can enhance the immune responses of innate immune cells to microbial pathogens. Mycobacterium bovis Bacillus Calmette-Guérin (BCG) and β-glucan (the main cell wall component of Candida albicans) can activate the nuclear factor-κB (NF-κB) pathway of innate immune cells or dendritic cell-associated C-type lectin 1/protein kinase B/mammalian target of rapamycin/hypoxia-inducible factor 1-alpha (Dectin-1/Akt/mTOR/HIF-1α) signaling pathway to regulate the metabolic reprogramming and epigenetic reprogramming, thereby inducing trained immunity. The discovery of trained immunity in innate immune cells provides a new direction for the research and development of new vaccines, the treatment strategies of immune deficiency, and the regulation of autoinflammatory diseases. Therefore, understanding the cytological mechanisms of trained immunity is of great significance for the prevention of unknown diseases.

Key words:trained immunity;innate immune cells;Bacillus Calmette-Gué;rin (BCG)