Innate Immune Memory: The Latest Frontier of Adjuvanticity

Figure 1

Main mechanisms involved in trained immune memory. In the picture the main mechanisms believed to underlie innate memory are shown. (a) Altered PRR expression. Phenotypic changes of innate immune cells with memory properties involve increased expression of PRRs on the cell surface and improved pathogen recognition. (b) Metabolic reprogramming. Innate immune memory requires a metabolic shift, which involves Warburg metabolism. The metabolism of glucose is shifted toward increased glycolysis with production of lactate and decreased oxidative phosphorylation. (c) Epigenetic reprogramming. Trimethylation of H3 at lysine 4 (H3K4me3) is a marker of promoter activation for proinflammatory genes specifically induced by β-glucan-dependent memory. (d) Altered cytokines release. Trained memory responses are characterised by an enhanced protective inflammatory reaction. The different patterns of cytokine release may be involved in the systemic establishment of a memory phenotype, reaching far/secluded anatomical sites (as suggested for brain responses and demonstrated in plants).