Trained immunity in respiratory diseases: Mechanisms of action and intervention strategies

Trained immunity refers to a form of nonspecific immunological memory established through epigenetic modifications and metabolic reprogramming in innate immune cells following stimulation. This concept offers a novel framework for understanding and treating respiratory diseases. Chronic inflammation and dysregulated immune memory resulting from respiratory immune imbalance underlie many respiratory conditions, including infectious pneumonia, asthma, and chronic obstructive pulmonary disease (COPD). The core mechanisms of trained immunity involve epigenetic regulation-mediated by histone modifications such as histone H3 lysine 4 trimethylation (H3K4me3)-and metabolic reprogramming, exemplified by glycolysis. Trained immunity exhibits a "double-edged sword" effect in respiratory diseases: appropriate activation enhances pathogen clearance, whereas excessive activation may lead to sustained inflammation and tissue damage. Intervention strategies targeting trained immunity-such as vaccine-induced training, metabolic modulation, and natural product application-have shown clinical promise. However, the field faces challenges, including a lack of specific regulatory approaches and clinically applicable biomarkers. Future efforts should focus on deepening mechanistic insights and facilitating the clinical translation of precise interventions, thereby opening new paradigms for the prevention and treatment of respiratory diseases.