de Araujo Ana Carolina V S C, Mambelli Fábio, Sanches Rodrigo O, Marinho Fábio V, Oliveira Sergio C
Departamento de Genética, Ecologia e Evolução, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, MG, Brazil.
Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo 05508-900, SP, Brazil.
Pathogens. 2023 Nov 24;12(12):1386. doi: 10.3390/pathogens12121386.
The bacillus Calmette-Guérin (BCG) is an attenuated bacterium derived from virulent . 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.
卡介苗（BCG）是一种源自强毒株的减毒细菌。它是唯一被许可用于预防儿童重症结核病的疫苗。除了对结核病的特定作用外，在人类和小鼠中，接种卡介苗后在异源刺激下还会产生有益的非特异性效应（NSEs）。卡介苗产生的非特异性效应可能与适应性免疫反应和先天性免疫反应都有关。后者也被称为训练免疫（TI），这是最近描述的先天性细胞的一种生物学特性，它能够基于代谢和表观遗传重编程实现功能改善。目前，与卡介苗介导的训练免疫相关的机制是深入研究的重点，但仍有许多空白需要阐明。本综述讨论了目前对卡介苗诱导的训练免疫的理解，探讨了对造血干细胞和单核细胞/巨噬细胞谱系中训练表型至关重要的信号通路。它重点关注卡介苗介导的训练免疫机制，包括这些细胞中针对细胞内病原体的代谢 - 表观遗传轴和炎性小体途径。此外，本研究还探讨了不同免疫细胞类型中的训练免疫、其预防各种细胞内感染的能力，以及训练后的先天性记忆与适应性记忆的整合，以塑造下一代疫苗。
