Innate immune memory, the missing piece of the immunological response

Abstract In the last decade, growing evidence has shed some light into an unrecognized capacity of the innate immune compartment: the unexpected ability of innate cells to enhance its response upon an immunological re-challenge. This capacity is called Trained immunity and resembles adaptive immune memory but lacks the specificity of antigen recognition by lymphocytes. Mechanistically, this type of memory or trained immunity, unlike somatic recombination or hypermutation of antigen-specific receptors in the adaptive memory; depends on pattern recognition receptors and metabolic changes that lead to long-term modifications on the epigenetic landscape, poising chromatin to readily express inflammatory cytokines upon a pathogenic re-challenge. In this review we will summarize and discuss the current progress made at elucidating the different innate cell populations with memory-like features, their receptors, downstream molecules and effector cytokines involved in the development and maintenance of trained immunity. This novel evidence overrides a very important dogma in immunology dissolving the boundaries separating innate and adaptive compartments of the immune system, and sets immunological memory as a shared mechanism of all immune cell types able to provide long-term protection to the host.