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Review
. 2023 Feb 10;21(1):106.
doi: 10.1186/s12967-023-03944-8.

BCG-induced trained immunity: history, mechanisms and potential applications

Jingjing Chen #  1   2 , Li Gao #  1   2 , Xinya Wu #  1   3 , Yuxin Fan  1   3 , Meixiao Liu  1   3 , Li Peng  1   2 , Jieqin Song  1   3 , Bingxue Li  1   3 , Aihua Liu  4   5   6 , Fukai Bao  7   8   9
Affiliations
Review

BCG-induced trained immunity: history, mechanisms and potential applications

Jingjing Chen et al. J Transl Med. .

Abstract

The Bacillus Calmette-Guérin (BCG) vaccine was discovered a century ago and has since been clinically applicable. BCG can not only be used for the prevention of tuberculosis, but also has a non-specific protective effect on the human body called trained immunity that is mediated by innate immune cells such as monocytes, macrophages, and natural killer cells. Mechanisms of trained immunity include epigenetic reprogramming, metabolic reprogramming, and long-term protection mediated by hematopoietic stem cells. Trained immunity has so far shown beneficial effects on cancer, viral-infections, autoimmune diseases, and a variety of other diseases, especially bladder cancer, respiratory viruses, and type 1 diabetes. The modulation of the immune response by BCG has led to the development of a variety of recombinant vaccines. Although the specific mechanism of BCG prevention on diseases has not been fully clarified, the potential role of BCG deserves further exploration, which is of great significance for prevention and treatment of diseases.

Keywords: BCG; Cancer; Epigenetic reprogramming; Metabolic reprogramming; Trained immunity; Viral infection.

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Conflict of interest statement

We declare no competing interests.

Figures

Fig. 1
Fig. 1
BCG and the history of trained immunity
Fig. 2
Fig. 2
BCG induces trained immunity by binding to NOD2 receptors. The Akt/mTOR pathway is then activated for the metabolic switch to glycolysis. BCG induces epigenetic and metabolic reprogramming of innate immune cells to train innate immunity. Epigenetic reprogramming and metabolic reprogramming influence each other. Through the interaction with hematopoietic stem cells, it plays a long-term protective effect against infection. When the body was stimulated by BCG again, the cells after the training immunization produced more pro-inflammatory factors
See this image and copyright information in PMC

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