The immune system’s challenge: (Re)-programming of cells and tissues to best protect from future insult

It is now widely accepted that, instead of uniformly responding to a given insult, innate immune cells undergo continuous cellular (re)-programming that adapts their immune sensing capabilities to their local tissue environment and to past pathogen exposures. To describe, characterize and molecularly comprehend these processes, we propose a Network Immunoscience Theory with ‘adaptation’
processes and ‘trained immunity’ (also termed ‘innate immune memory’) being two major cellular programming mechanisms. Reprogramming comprises epigenetic imprinting, the wiring of signaling pathways and the expansion and re-localization of cellular subsets equipped with those specific functions. 

A thematic overview of the two key areas cellular and molecular ‘adaptation’ of innate immune cells, and molecular regulation and the role of ‘trained immunity’ in disease, is provided in the following figure.