Host Defense Peptides: Front-Line Immunomodulators

Trends Immunol. 2014 Sep;35(9):443-50. doi: 10.1016/ Epub 2014 Aug 8.


Although first studied for their antimicrobial activity, host defense peptides (HDPs) are now widely recognized for their multifunctional roles in both the innate and adaptive immune responses. Their diverse immunomodulatory capabilities include the modulation of pro- and anti-inflammatory responses, chemoattraction, enhancement of extracellular and intracellular bacterial killing, cellular differentiation and activation of the innate and adaptive compartments, wound-healing, and modulation of autophagy as well as apoptosis and pyroptosis. We review the various immunomodulatory roles of HDPs and their synthetic analogs, the innate defense regulators (IDRs). We discuss their potential as host-directed therapies, the hurdles they face in clinical development, and propose ways forward.

Publication types

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

MeSH terms

  • Adaptive Immunity
  • Animals
  • Antimicrobial Cationic Peptides / physiology*
  • Apoptosis
  • Autophagy
  • Chemotaxis
  • Humans
  • Immunity, Innate
  • Immunomodulation*
  • Molecular Targeted Therapy*


  • Antimicrobial Cationic Peptides