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The concept that only adaptive immunity can build immunological memory has been challenged in the past decade. Live attenuated vaccines such as the Bacillus Calmette-Guérin, measles-containing vaccines, and the oral polio vaccine have been shown to reduce overall mortality beyond their effects attributable to the targeted diseases. After an encounter with a primary stimulus, epigenetic and metabolic reprogramming of bone marrow progenitor cells and functional changes of tissue immune cell populations result in augmented immune responses against a secondary challenge. This process has been termed trained immunity. This review describes the mechanisms leading to trained immunity and summarizes the most important developments from the past few years., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The paradigm that only adaptive immunity can develop immunological memory has recently been challenged by studies showing that cells from the innate immune system can undergo functional reprogramming, facilitating a faster and enhanced response to secondary infections. This improved secondary response is not always specific, as it can also protect from infections caused by non-related pathogens. This has been termed innate immune memory or trained immunity. Trained immunity not only involves rewiring the intracellular immune signaling of innate immune cells, but also induces profound changes in cellular metabolic pathways such as glycolysis, oxidative phosphorylation, fatty acid and amino acid metabolism, increasing the capacity of the innate immune cells to respond to a secondary stimulation. The understanding of these intracellular processes opens new therapeutic possibilities for the modulation of the innate immune responses during infections and inflammatory diseases., (Copyright © 2018 Elsevier Ltd. All rights reserved.)