Prophylactic and therapeutic insights into trained immunity: A renewed concept of innate immune memory

Abstract

Trained immunity is a renewed concept of innate immune memory that facilitates the innate immune system to have the capacity to remember and train cells via metabolic and transcriptional events to enable them to provide nonspecific defense against the subsequent encounters with a range of pathogens and acquire a quicker and more robust immune response, but different from the adaptive immune memory. Reversing the epigenetic changes or targeting the immunological pathways may be considered potential therapeutic approaches to counteract the hyper-responsive or hypo-responsive state of trained immunity. The efficient regulation of immune homeostasis and promotion or inhibition of immune responses is required for a balanced response. Trained immunity-based vaccines can serve as potent immune stimuli and help in the clearance of pathogens in the body through multiple or heterologous effects and confer protection against nonspecific and specific pathogens. This review highlights various features of trained immunity and its applications in developing novel therapeutics and vaccines, along with certain detrimental effects, challenges as well as future perspectives.

Training vs. Tolerance: The Yin/Yang of the Innate Immune System

“…Pre-exposure to specific DAMPs as non-microbial triggers can induce the functional reprogramming of innate immune cells triggering an altered immune response toward a subsequent challenge [ 117 ]. DAMPs released during tissue injury from cell death or after organ transplantation allow innate immune cells to elicit long-term epigenetic changes at the promoters of inflammatory genes and cause metabolic rewiring [ 24 , 119 ]. Vimentin and HMGB1 represent inflammatory mediators upregulated during organ transplantation, responsible for acute and chronic transplant rejection [ 120 , 121 ].…”

Drosophila melanogaster as a model to study innate immune memory

“…Transcriptional and epigenetic modifications, accompanied and regulated by induced metabolic changes, happening in innate immune cells when exposed to stimulus (Boraschi and Italiani, 2018;Bindu et al, 2022). Non-specific acquired resistance/Trained potentiation Priming-induced enhancement of the innate immune response to subsequent challenges (Boraschi and Italiani, 2018).…”

“…The first exposure of the host to the challenge is defined by the authors in the field as priming ( Cooper and Eleftherianos, 2017 ; Sheehan et al, 2020 ). As perfectly detailed in the review by Bindu et al (2022) , the innate immune reprogramming happening after priming is given via epigenetic and metabolic modifications of trained cells which can lead either to an increase or a decrease in immunity ( Boraschi and Italiani, 2018 ). The mechanisms of this reprogramming are not completely understood yet, though some evidence supports the existence of multiple regulators ( Ghisletti et al, 2010 ; Smale et al, 2014 ; Fanucchi et al, 2019 ; Natoli and Ostuni, 2019 ).…”

A "trained immunity" inducer-adjuvanted nanovaccine reverses the growth of established tumors in mice

“…Accumulated data have shown that innate immune cells undergo long-term transcriptomic, metabolic and epigenetic rewiring to adjust their functional program and display memory-like characteristics in a process termed ''trained immunity'' [3]. Innate immune cells are trained in response to specific initial stimuli, and these trained cells produce a more rapid and stronger response to secondary homologous or even heterologous stimuli, indicating enhanced immune responses, such as proinflammatory cytokine and ROS expression [4].…”