Signal-Strength and History-Dependent Innate Immune Memory Dynamics in Health and Disease

Handb Exp Pharmacol. 2022:276:23-41. doi: 10.1007/164_2021_485.

Abstract

Innate immunity exhibits memory characteristics, reflected not only in selective recognition of external microbial or internal damage signals, but more importantly in history and signal-strength dependent reprogramming of innate leukocytes characterized by priming, tolerance, and exhaustion. Key innate immune cells such as monocytes and neutrophils can finely discern and attune to the duration and intensity of external signals through rewiring of internal signaling circuitries, giving rise to a vast array of discreet memory phenotypes critically relevant to managing tissue homeostasis as well as diverse repertoires of inflammatory conditions. This review will highlight recent advances in this rapidly expanding field of innate immune programming and memory, as well as its translational implication in the pathophysiology of selected inflammatory diseases.

Keywords: Exhaustion; Inflammatory diseases; Innate immunity; Innate memory; Memory dynamics; Priming; Signal strength; Tolerance.

Publication types

  • Review

MeSH terms

  • Humans
  • Immune Tolerance
  • Immunity, Innate*
  • Immunologic Memory*
  • Monocytes
  • Signal Transduction