Multifaceted roles of trained immunity in diverse pathological contexts

Abstract

Trained immunity, an innate immune response characterized by enhanced cellular responsiveness, exhibits a profound memory akin to adaptive immunity. This phenomenon involves intricate metabolic and epigenetic reprogramming triggered by stimuli such as β-glucan and BCG, shaping innate immune memory. Following elucidation of the background on trained immunity, it is important to explore its multifaceted roles in various pathological contexts. In this review, we delve into the specific contributions of trained immunity in the intricate landscape of viral infections, tumorigenesis, and diverse inflammatory diseases, shedding light on its potential as a therapeutic target, and offering comprehensive understanding of its broader immunological implications. [BMB Reports 2024; 57(10): 431-440].

Fig. 1

Epigenetic reprogramming during trained immunity. Innate immune cells, when exposed to stimuli like β-glucan, BCG, undergo epigenetic reprogramming. This leads to the initial activation of genes, marked by the accumulation of specific epigenetic markers such as H3K4me3 at gene promoters, H3K4me1 at enhancer. Some of these markers, like H3K4me1, remain even after the initial stimulus is gone (priming of enhancer/promoter). As a result of this epigenetic reprogramming, if the cells encounter a secondary stimulus, the transcription of immune genes is significantly enhanced. Figure was illustrated by Biorender (https://biorender.com/) accessed on 10th May 2024. BCG, Bacillus Calmette-Guérin; ATAC, Assay for Transposase-Accessible Chromatin.

Fig. 2

Interplay between metabolic and epigenetic rewiring during the trained immunity process. Various pathogens, vaccines, and stimuli can cause long-lasting changes in the functionality, metabolism, and epigenetic profiles of innate immune cells. Trained immunity enables an improved response upon a subsequent encounter with either the same or different pathogens, thereby providing broad-spectrum protection. The signaling pathway involving trained immunity activates mTOR-HIF1α signaling pathway, modifying the activity of various intracellular pathways. This results in the enhanced production of metabolites and co-factors necessary for the functioning of epigenetic enzymes, leading to changes in the chromatin and DNA’s epigenetic landscape. These alterations in gene expression play a pivotal role in the development of trained immunity. This figure was illustrated by Biorender (https://biorender.com/), accessed on 26th Mar 2024. BCG, Bacillus Calmette-Guérin; ILC, Innate lymphoid cell; DC, Dendritic cell; NK cell, Natural killer cell; ATP, Adenosine triphosphate; α-KG, α-Ketoglutarate; PRC, Polycomb repressive complex; Me, Methylation; TF, Transcription factor; RNAPII, RNA polymerase II; PRRs, Pattern recognition receptors; DAMPs, Damage-Associated Molecular Patterns; PAMPs, Pathogen-Associated Molecular Patterns.