Transcriptional Regulation of Antimicrobial Host Defense Peptides

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.