Resolving trained immunity with systems biology

Trained immunity is characterized by long-term functional reprogramming of innate immune cells following challenge with pathogens or microbial ligands during infection or vaccination. This cellular reprogramming leads to increased responsiveness upon restimulation, and is mediated through epigenetic and metabolic modifications. In this review, we describe how molecular mechanisms underlying trained immunity, for example, induced by beta-glucan or Bacille Calmette-Guerin (BCG) vaccination, can be investigated by using and integrating different layers of information including genome, epigenome, transcriptome, proteome, metabolome, microbiome, immune cell phenotyping, and function. We also describe the most commonly used experimental and computational techniques. Finally, we provide a number of examples of how a systems biology approach was applied to study trained immunity to understand interindividual variation or the complex interplay between molecular layers. In conclusion, trained immunity represents an opportunity for regulating innate immune function, and understanding the complex interplay of mechanisms that mediate trained immunity might enable us to employ it as a clinical tool in the future.

Automated summary

Trained immunity involves long-term functional reprogramming of innate immune cells, leading to enhanced responsiveness to pathogens or microbial ligands. Investigating the molecular mechanisms underlying trained immunity through various layers of information using a systems biology approach can help understand the complex interplay between molecular layers and individual variation.