Cationic host defence peptides: multifaceted role in immune modulation and inflammation

Abstract

Host defence peptides (HDPs) are innate immune effector molecules found in diverse species. HDPs exhibit a wide range of functions ranging from direct antimicrobial properties to immunomodulatory effects. Research in the last decade has demonstrated that HDPs are critical effectors of both innate and adaptive immunity. Various studies have hypothesized that the antimicrobial property of certain HDPs may be largely due to their immunomodulatory functions. Mechanistic studies revealed that the role of HDPs in immunity is very complex and involves various receptors, signalling pathways and transcription factors. This review will focus on the multiple functions of HDPs in immunity and inflammation, with special reference to cathelicidins, e.g. LL-37, certain defensins and novel synthetic innate defence regulator peptides. We also discuss emerging concepts of specific HDPs in immune-mediated inflammatory diseases, including the potential use of cationic peptides as therapeutics for immune-mediated inflammatory disorders.

Fig. 1

Mechanism of immunomodulatory activity of LL-37 and IDR-1. Intracellular uptake of LL-37 and IDR-1 is hypothesized to be mediated by an atypical endocytic process. Interaction of these peptides with intracellular receptors such as GAPDH and sequestosome (SQSTM)-1 facilitates alteration of pathogen- or inflammatory mediator-induced signalling pathways, leading to alteration of transcription factor activity with different kinetics. The overall downstream effect is selective control of inflammatory responses and enhanced pathogen clearance. Modified from Mookherjee et al. [35, 40] and Yu et al. [41].