The Intersection of Epigenetics and Metabolism in Trained Immunity

Stephanie Fanucchi,Jorge Domínguez-Andrés,Leo A.B Joosten,Mihai G Netea,Musa M Mhlanga

doi:10.1016/j.immuni.2020.10.011

Abstract

The last few years have witnessed an increasing body of evidence that challenges the traditional view that immunological memory is an exclusive trait of the adaptive immune system. Myeloid cells can show increased responsiveness upon subsequent stimulation with the same or a different stimulus, well after the initial challenge. This de facto innate immune memory has been termed "trained immunity" and is involved in infections, vaccination and inflammatory diseases. Trained immunity is based on two main pillars: the epigenetic and metabolic reprogramming of cells. In this review we discuss the latest insights into the epigenetic mechanisms behind the induction of trained immunity, as well as the role of different cellular metabolites and metabolic networks in the induction, regulation and maintenance of trained immunity.

Highlights

The vertebrate immune system has been divided into two main branches: the adaptive immune system and the innate immune system
The innate immune system constitutes a first line of defense that recognizes stimuli of a different nature, eliciting a non-specific, rapid, protective response against pathogens (Medzhitov and Janeway, 2000)
This study provided evidence that lncRNA-mediated regulation is central to the mechanism of how H3K4me3 chromatin marks are established during trained immunity

Summary

Introduction

The vertebrate immune system has been divided into two main branches: the adaptive immune system and the innate immune system. In contrast to trained immunity, when the stimulation ceases, tolerized cells undergo a functional program characterized by the epigenetic silencing of inflammatory genes and that regulate the immune response are still poorly understood. The stimulation of innate immune cells involves the activation of diverse intracellular pathways that result in the upregulation of proinflammatory gene transcription and the production of proinflammatory cytokines and chemokines (Liu et al, 2017).

Results

Conclusion