PDF(Pubmed)
Abstract：
The bacillus Calmette-Guérin (BCG) is an attenuated bacterium derived from virulent Mycobacterium bovis. It is the only licensed vaccine used for preventing severe forms of tuberculosis in children. Besides its specific effects against tuberculosis, BCG administration is also associated with beneficial non-specific effects (NSEs) following heterologous stimuli in humans and mice. The NSEs from BCG could be related to both adaptive and innate immune responses. The latter is also known as trained immunity (TI), a recently described biological feature of innate cells that enables functional improvement based on metabolic and epigenetic reprogramming. Currently, the mechanisms related to BCG-mediated TI are the focus of intense research, but many gaps are still in need of elucidation. This review discusses the present understanding of TI induced by BCG, exploring signaling pathways that are crucial to a trained phenotype in hematopoietic stem cells and monocytes/macrophages lineage. It focuses on BCG-mediated TI mechanisms, including the metabolic-epigenetic axis and the inflammasome pathway in these cells against intracellular pathogens. Moreover, this study explores the TI in different immune cell types, its ability to protect against various intracellular infections, and the integration of trained innate memory with adaptive memory to shape next-generation vaccines.
摘要：
卡介苗（BCG）是一种减毒细菌，源自牛分枝杆菌。它是用于预防儿童严重结核病的唯一许可疫苗。除了它对结核病的具体影响，在人和小鼠中异源刺激后,BCG施用还与有益的非特异性效应(NSE)相关。来自BCG的NSE可能与适应性和先天免疫反应有关。后者也被称为训练免疫（TI）。最近描述的先天细胞的生物学特征，能够基于代谢和表观遗传重编程来改善功能。目前,与BCG介导的TI相关的机制是紧张研究的焦点，但是许多差距仍然需要阐明。这篇综述讨论了目前对BCG诱导TI的理解，探索对造血干细胞和单核细胞/巨噬细胞谱系的训练表型至关重要的信号通路。它侧重于BCG介导的TI机制，包括代谢-表观遗传轴和这些细胞中对抗细胞内病原体的炎性小体途径。此外，这项研究探讨了不同免疫细胞类型中的TI，它具有防止各种细胞内感染的能力，以及将经过训练的先天记忆与适应性记忆相结合，以塑造下一代疫苗。
