Title:Transcriptional Regulation of Antimicrobial Host Defense Peptides
Volume: 16
Issue: 7
Author(s): Wentao Lyu, Amanda R. Curtis, Lakshmi T. Sunkara and Guolong Zhang
Affiliation:
Keywords:
Antibiotic alternatives, antimicrobial resistance, cathelicidins, defensins, host defense peptides, nutritional regulation.
Abstract: Host defense peptides (HDPs) are of either myeloid or epithelial origin with antimicrobial
and immunomodulatory functions. Due to HDP’s ability to physically disrupt bacterial cell membranes
and profoundly regulate host innate and adaptive immunity, microbial resistance to these peptides is
rare. As an important first line of defense, HDPs are mostly present in epithelial cells of the digestive,
respiratory or urogenital tracts as well as in the granules of neutrophils, macrophages or intestinal secretory
Paneth cells. HDPs are either directly released or inducibly expressed upon exposure to microbes or microbial
products, although certain pathogens such as Shigella have evolved an ability to down-regulate HDP synthesis as an immune
invasion strategy. Even if a majority of HDPs are induced by infection and inflammation, it is undesirable to augment
HDP synthesis and host immunity using pathogen-associated molecular patterns because of an excessive inflammation
that is usually accompanied. Recently, several different classes of small-molecule compounds have been identified
with the capacity to specifically induce HDP synthesis without triggering extensive inflammatory response. A few HDPinducing
compounds even synergize with each other in HDP induction. In this review, we summarized the recent progresses
on transcriptional regulation of HDPs by infection and inflammation and by small-molecule compounds. We suggested
the potential of dietary regulation of HDPs as a novel antibiotic-alternative strategy to antimicrobial therapy, as
oral supplementation of HDP-inducing compounds has shown promise of preventing and controlling infections in humans
and several animal species.
