Trained immunity

Trained immunity, a concept developed primarily by Mihai Netea and colleagues, refers to the capacity of innate immune cells — principally monocytes, macrophages, and NK cells — to mount enhanced, non-specific responses to secondary stimuli following an initial training event, without invoking classical adaptive immunological memory. The mechanism involves epigenetic reprogramming (histone acetylation and methylation at promoters of inflammatory genes) and metabolic rewiring toward aerobic glycolysis, which together lower the activation threshold of the cell for weeks to months. Well-characterised inducers include β-glucan (a fungal cell-wall component) and the BCG tuberculosis vaccine, which have been shown to reduce heterologous infections and all-cause mortality in some controlled trials. Trained immunity is distinct from the somatic hypermutation and clonal selection that define B- and T-cell memory, and it represents an epigenetic memory in the innate arm of immunity.