Trained immunity has emerged as a paradigm-shifting concept in immunology, challenging the long-held view that only the adaptive immune system generates long-lasting immune memory. This phenomenon demonstrates that innate immune cells can undergo memory-like reprogramming, enabling enhanced and nonspecific responses to subsequent challenges. The Bacillus Calmette-Guérin (BCG) vaccine, a cornerstone in tuberculosis (TB) prevention, is one of the most extensively studied inducers of trained immunity. Recent research reveals that BCG induces epigenetic and metabolic reprogramming of innate immune cells, providing protection against different diseases beyond TB. This narrative review explores the molecular and cellular mechanisms underlying BCG-induced trained immunity and its broad clinical applications. By integrating recent findings with clinical perspectives, this review highlights the transformative potential of this phenomenon, offering novel therapeutic strategies to improve global health.
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