The changes to the innate immune response may last up to several months, in contrast to the classical immunological memory (which may last up to a lifetime), and is usually unspecific because there is no production of specific antibodies/receptors.
[12] Similarly, Candida albicans and fungal β-glucan trigger changes in monocyte histone methylation, this functional reprogramming eventually provides protection against reinfection.
[7] Though the epigenetic modification is beneficial to the innate immune system response, it can impair macrophage resolution pathways- promoting unfavorable tissue remodeling at the inflammatory site.
[19] Trained immunity can shift macrophages toward a pro-inflammatory glycolytic M1 phenotype by an Akt/mTor HIF1α dependent pathway, away from the M2 phenotype in which macrophages maintain the Krebs cycle and oxidative phosphorylation[20][21] The trained immunity involving NK cells looks more like classic immunological memory, because there is development of at least partially-specific clones of NK cells.
[22] Reinfection of memory NK cells in mouse led to an enhanced cytokine production by Ly49H receptor with a more specific response to pathogen.
[30] Lung specific ILC2 showed memory-like phenotype after allergen exposure[31] Trained immunity relies on epigenetic reprogramming which leads to a stronger and rapid response to recurrent triggers.
Long non-coding RNAs (lncRNAs) are also critical to epigenetic reprogramming, such as their role in the assignment of H3K4me3 markers to genome which modulates gene expression.
[35] Subsequently, a cross-talk between glycolysis, glutaminolysis and cholesterol synthesis pathways was demonstrated as essential for trained immunity – β-glucan-triggered monocytes.