BCG-induced trained immunity in NK cells: Role for non-specific protection to infection

• BCG vaccination induces trained immunity in NK cells.
• Main difference with ‘memory’ NK cells is non-specific effects by trained immunity.
• Trained immunity in NK cells induces increased pro-inflammatory cytokine production.
• The effects of trained immunity last up to three months.
• There was not a specific cell type identified responsible for these effects.

Adaptive features of innate immunity, also termed ‘trained immunity’, have recently been shown to characterize monocytes of BCG vaccinated healthy volunteers. Trained immunity leads to increased cytokine production in response to non-related pathogens via epigenetic reprogramming of monocytes. Recently, memory-like properties were also observed in NK cells during viral infections, but it is unknown if memory properties of NK cells contribute to trained immunity due to BCG vaccination.BCG vaccination of healthy volunteers increased proinflammatory cytokine production following ex vivo stimulation of NK cells with mycobacteria and other unrelated pathogens up until at least three months after vaccination. In addition, in a murine model of disseminated candidiasis, BCG vaccination led to an increased survival in SCID mice, which was partially dependent on NK cells.These findings suggest that NK cells may contribute to the non-specific (heterologous) beneficial effects of BCG vaccination.