Long-term Reprogramming of the Innate Immune System

During the last few years, a growing body of evidence has shown that immunological memory is not an exclusive trait of lymphocytes, as many inflammatory insults can alter the functionality and the responsiveness of the innate immune system in the long term. Innate immune cells, such as monocytes, macrophages, dendritic cells, and NK cells can be influenced by the encounters with inflammatory stimuli, undergoing functional reprogramming and developing changed responses to subsequent chellenges. The long-term reprogramming depends on the rewiring of cell metabolism and epigenetic processes, and they stay at the basis of induction of both innate immune memory (also termed trained immunity) and innate immune tolerance. Here, we review the central role that the effects of this long-term reprogramming of innate immune cells plays in a number of clinically relevant conditions such as vaccination, atherosclerosis, sepsis, and cancer.