Training innate immunity: the changing concept of immunological memory in innate host defence

The inability of innate immunity to build an immunological memory is considered a main difference with adaptive immunity. This concept has been challenged by studies in plants, invertebrates and mammals. Recently, a paradigm shift in our understanding host defence has been triggered by the mounting evidence for innate immune memory, leading to increased responses to secondary infections. Important differences between the cell populations and the molecular mechanisms exist between the adaptive traits of innate host defence on the one hand and immunological memory of adaptive immunity on the other hand. The lasting state of enhanced innate immunity termed 'trained immunity' is mediated by prototypical innate immune cells such as natural killer cells and monocytes/macrophages. It provides protection against reinfection in a T/B-cell-independent manner, with both specific mechanisms and nonspecific epigenetic reprogramming mediating these effects. This concept represents a paradigm change in immunity, and its putative role in resistance to reinfection may represent the next step in the design of future vaccines.