Human α-Defensin 6 Promotes Mucosal Innate Immunity Through Self-Assembled Peptide Nanonets

TLDR

Antimicrobial peptides, especially α‑defensins, are key intestinal innate immunity components; while HD5 is bactericidal, HD6’s role was unknown until Chu et al. demonstrated its protective effect against bacterial pathogens.

Abstract

Netting the Bad Guys Antimicrobial peptides are an evolutionarily conserved component of innate immunity in the intestine. One family, α-defensins, typically exert their antimicrobial effects through microbicidal activity against bacteria. Humans express only two α-defensins, human defensin 5 (HD5) and HD6. HD5 exhibits bactericidal activity and plays a role in shaping the bacterial composition of the gut. HD6, on the other hand, does not show bactericidal activity and its function in the gut is unclear. Now, Chu et al. (p. 477 , published online 21 June; see the Perspective by Ouellette and Selsted ) show that HD6 protects against bacterial pathogens. Rather than killing them directly, HD6 binds to bacteria surface proteins and, through a process of self-assembly, forms fibrils and nanonets that ensnare invading bacterial pathogens.