Trained Immunity: Reprogramming Innate Immunity in Health and Disease

Annu Rev Immunol. 2021 Apr 26:39:667-693. doi: 10.1146/annurev-immunol-102119-073855. Epub 2021 Feb 26.

Abstract

Traditionally, the innate and adaptive immune systems are differentiated by their specificity and memory capacity. In recent years, however, this paradigm has shifted: Cells of the innate immune system appear to be able to gain memory characteristics after transient stimulation, resulting in an enhanced response upon secondary challenge. This phenomenon has been called trained immunity. Trained immunity is characterized by nonspecific increased responsiveness, mediated via extensive metabolic and epigenetic reprogramming. Trained immunity explains the heterologous effects of vaccines, which result in increased protection against secondary infections. However, in chronic inflammatory conditions, trained immunity can induce maladaptive effects and contribute to hyperinflammation and progression of cardiovascular disease, autoinflammatory syndromes, and neuroinflammation. In this review we summarize the current state of the field of trained immunity, its mechanisms, and its roles in both health and disease.

Keywords: epigenetics; immunometabolism; innate immune memory; innate immune system; trained immunity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Differentiation
  • Humans
  • Immune System
  • Immunity, Innate
  • Immunologic Memory*
  • Vaccines*

Substances

  • Vaccines