Fig. 1 |. Trained immunity and tolerance: two opposite functional programmes of innate immunity.

Infections or sterile tissue triggers induce inflammation and the activation of immune effector mechanisms. Concomitant to a proinflammatory response, anti-inflammatory mechanisms are provoked to prevent overshooting inflammation and tissue damage and to limit the inflammatory response in time. Trained immunity involves epigenetic and metabolic reprogramming of the innate immune cells, allowing qualitatively and quantitatively adjusted responses of innate immune cells to subsequent time-delayed heterologous stimulation. Misguided trained immunity responses can contribute to disease progression, resulting in either a chronic hyperinflammatory state or a persistent state of immunological tolerance, a mechanism that dampens the inflammatory response of the host to maintain homeostasis and prevent tissue damage and organ failure, with the subsequent risk of secondary infections and other diseases related to decreased activity of the immune system.