Avian Antimicrobial Host Defense Peptides: From Biology to Therapeutic Applications

Abstract

Host defense peptides (HDPs) are an important first line of defense with antimicrobial and immunomoduatory properties. Because they act on the microbial membranes or host immune cells, HDPs pose a low risk of triggering microbial resistance and therefore, are being actively investigated as a novel class of antimicrobials and vaccine adjuvants. Cathelicidins and β-defensins are two major families of HDPs in avian species. More than a dozen HDPs exist in birds, with the genes in each HDP family clustered in a single chromosomal segment, apparently as a result of gene duplication and diversification. In contrast to their mammalian counterparts that adopt various spatial conformations, mature avian cathelicidins are mostly α-helical. Avian β-defensins, on the other hand, adopt triple-stranded β-sheet structures similar to their mammalian relatives. Besides classical β-defensins, a group of avian-specific β-defensin-related peptides, namely ovodefensins, exist with a different six-cysteine motif. Like their mammalian counterparts, avian cathelicidins and defensins are derived from either myeloid or epithelial origin expressed in a majority of tissues with broad-spectrum antibacterial and immune regulatory activities. Structure-function relationship studies with several avian HDPs have led to identification of the peptide analogs with potential for use as antimicrobials and vaccine adjuvants. Dietary modulation of endogenous HDP synthesis has also emerged as a promising alternative approach to disease control and prevention in chickens.

The first report of a Pelecaniformes defensin cluster: Characterization of β-defensin genes in the crested ibis based on BAC libraries

“…This could be mainly attributed to the immature immune system of the developing embryos and newly hatched chicks, since components of the adaptive response are in a naïve state44. Many avian studies have demonstrated that avian defensins can protect embryos and nestlings from potential pathogenic assault and promote the early transition from an innate immune response to an adaptive one111245. Thus, some studies utilized defensin genes as genetic markers to select for resistance to certain infections and thereby enhance the innate immune response via selective breeding in poultry4546, while some others adopted artificially regulated defensin expression via maternal diet, for example, to control the selective colonization of birds and thereby suppress pathological microflora1147.…”

“…Defensins are a collection of small peptides (commonly less than 100 amino acids) enriched in hydrophobic and cationic residues1112 that play a critical role in regulating the innate immune systems13 of a wide range of organisms including fungi, plants, invertebrates, and vertebrates12141516. These antimicrobial peptides can protect the host against a broad spectrum of pathogens, such as bacteria, enveloped viruses, certain fungi, and parasitic protozoa1317, mainly by binding to and disturbing pathogen membranes, blocking viral replication cycles, or changing host cell recognition sites1318.…”

Expression of host defense peptides in the intestine of Eimeria-challenged chickens

“…In avians, 14 avian beta-defensins (AvBD), 4 cathelicidins (CATH), and liver expressed antimicrobial peptide-2 (LEAP2) have been identified as HDP (Cuperus et al, 2013;Zhang and Sunkara, 2014). In vitro studies showed some of these HDP have a direct negative effect on bacteria such as Campylobacter and Salmonella (Milona et al, 2007;Townes et al, 2009;van Dijk et al, 2012).…”

The Evolution of Innate Immune Genes: Purifying and Balancing Selection on β-Defensins in Waterfowl

“…Furthermore, HDPs are well characterized with respect to structure, function and activity (reviewed in Zasloff 2002;Yeaman and Yount 2003;Brogden 2005;Melo et al 2009;Nguyen et al 2011;Li et al 2012). HDPs are increasingly recognized as potential therapeutic agents, in some cases offering a potential alternative to conventional antibiotics to which resistance is a global problem (Hancock and Sahl 2006;Zhang and Sunkara 2014). An increased understanding of the evolutionary and molecular properties of these peptides is, therefore, crucial.…”

“…b-defensins are the only class of defensin in birds and are the most ancient of the three classes (van Dijk et al 2008); a-defensins are found exclusively in mammals and h-defensins in some primates (Ganz 2003;Zhang and Sunkara 2014). The fundamental importance of b-defensins in impeding pathogens has been demonstrated in humans (e.g., Quiñones-Mateu et al 2003;Wehkamp et al 2005;Hazrati et al 2006;Funderburg et al 2007;Jarczak et al 2013;Segat et al 2014), and to a lesser extent in birds (Soman et al 2009;Ma et al 2011).…”