The two human α-defensins HD5 and HD6, produced by the Paneth cells, play a pivotal role in defense against food- and water-borne pathogens in the intestine.
The mechanism by which these two α-defensins protect from enteric pathogens is quite distinct. HD5 is a potent antimicrobial that kills target microbes by membrane disruption, whereas HD6 is newly discovered to self-assemble to form fibrils and nanonets that surround and entangle bacteria.
Recent data suggest that HD5 also serves to help shape the composition of the colonizing microbiota. The activity of human β-defensins may determine the fate of several infections of the colon. hBD-2 has been shown to be highly effective in killing Gram-negative enteric E. coli and Pseudomonas aeruginosa and yeast Candida albicans, but it was only bacteriostatic against Gram-positive Staphylococcus aureus.
In the case of hBD-1, which is ubiquitously distributed and exhibits poor in vitro antimicrobial effect in its oxidative form. However, reduction of disulphide-bridges makes hBD-1 a potent
antimicrobial peptide against C. albicans and anaerobic Gram-positive commensals such as Bifidobacterium and Lactobacillus species. The in vivo killing capacity of β-defensin will depend on the local ionic concentration and presence of other innate components in the environment where the pathogen and antimicrobial peptide interacts. For instance, the presence of lysozyme and lactoferrin increases hBD-2 killing of E. coli, P. aeruginosa, Enterococcus faecalis and S. aureus.