This 2018 Netherlands review topic was the long-term epigenetic programming of the innate immune system:
“Immunological memory has been classically described for the adaptive immune system, in which naive B and T lymphocytes develop antigen-specific, long-lasting memory cells after encountering a new antigen.
Immunological memory is not an exclusive trait of lymphocytes. The function of cells from the innate immune system, such as monocytes, macrophages, dendritic cells, and NK cells, is also influenced by the contact with different stimuli, undergoing functional reprogramming.
β-glucan, the prototypical trained immunity-inducing agonist:
- Modulates hematopoietic stem and progenitor cells, influencing the behavior and responsiveness of peripheral myeloid cells;
- Leads to a shift of cellular metabolism from oxidative phosphorylation toward aerobic glycolysis.
Analysis of transcriptional data from macrophages stimulated with β-glucan revealed that the cholesterol synthesis pathway is highly up-regulated in trained immunity. A follow-up of this study showed that the activation of the cholesterol synthesis pathway, but not its synthesis itself, is crucial for innate memory. In agreement with this, the inhibition of cholesterol synthesis in mice reduced the induction of trained immunity by β-glucan.
β-glucan-induced changes in trimethylation of histone 3 lysine 4 (H3K4me3) and acetylation of histone 3 lysine 27 (H3K27ac) in human monocytes 7 days after the first stimulation in vitro were associated with a switch to glycolysis, suggesting a deep, long lasting reprogramming of the cells.
Inducers of cellular reprogramming such as β-glucan have shown potential as a treatment or adjuvant for osteosarcoma, influenza, or skin lesions, among others.”
https://jlb.onlinelibrary.wiley.com/doi/pdf/10.1002/JLB.MR0318-104R “Long-term reprogramming of the innate immune system” (not freely available)