Article Sharing | β-Defensins: Microbiota Regulators for Maintaining Homeostasis and Health – Introduction

β-Defensins: Microbiota Regulators for Maintaining Homeostasis and Health – Introduction

Reference
Meade KG, O’Farrelly C. β-Defensins: Farming the Microbiome for Homeostasis and Health. Front Immunol. 2019;9:3072. doi:10.3389/fimmu.2018.03072.

Statement

This article is a translated and condensed summary based on the above review article. The content has been reorganized for scientific communication and educational purposes and does not represent the complete views of the original publication. Readers are encouraged to consult the original article for comprehensive information.

Defensins are small cationic peptides widely distributed throughout the animal and plant kingdoms. Characterized by six conserved cysteine residues, defensins are classified into three subclasses: α-, β-, and θ-defensins. α-Defensins are believed to have evolved from β-defensins in certain mammals and are structurally distinguished by a different pattern of intramolecular disulfide bridges. Interestingly, while a large number of closely related functional α-defensins have been identified in the equine genome, they are largely absent in most artiodactyl species, including cattle. In contrast, only β-defensin genes have been identified in birds, and β-defensins are found in the genomes of all vertebrates examined to date, suggesting that this family originated early in vertebrate evolution. θ-Defensins, which are unique to primates, represent the most recently evolved subclass and are thought to have arisen from the fusion of α- and β-defensin sequences. Among the three subclasses, β-defensins have been the most extensively studied. Gene duplication and subsequent sequence diversification have generated a large β-defensin family in mammals. Despite considerable variation in amino acid sequences, these peptides share a highly conserved tertiary structure stabilized by intramolecular disulfide bonds. Owing to their abundance and biological importance in vertebrates, β-defensins are the focus of this review.

β-Defensin genes typically exhibit a characteristic two-exon organization, with the first exon encoding the signal and propeptide regions, while the second exon encodes the mature peptide containing the six-cysteine motif. Advances in genome sequencing and comparative genomics have greatly expanded the catalog of β-defensin genes and enabled the identification of species-specific evolutionary patterns. Current estimates range from 14 β-defensin genes in chickens to 29 in pigs, 38 in dogs, 33 in chimpanzees, and 48 in both mice and humans, although these numbers are expected to change as genome annotations improve and copy number variations are more accurately characterized. Comparative immunological studies have also identified amino acid sites under positive selection, which may contribute to functional divergence among species. Notably, the absence of a classical α-helical region in bovine β-defensins suggests distinct mechanisms of action and may partly explain the expansion of this family within ruminants. The loss of α-defensins and species-specific expansion of β-defensins in certain livestock species are becoming increasingly apparent and may offer opportunities for improving animal health.

From a functional perspective, characterization of β-defensin genes and peptides has been largely restricted to model organisms, including mice, rats, and humans. Although recent advances in sequencing technologies and genome assembly have revealed lineage-specific expansions in non-model species, many of these genes remain poorly characterized. Functional studies in non-model organisms provide insights into the selective pressures driving the dynamic evolution of β-defensin gene repertoires and highlight their potential as novel tools for infection control. Increasing evidence supports a close relationship between β-defensin genes and microbial diversity at mucosal surfaces. Given the growing interest in microbiome modulation and the prevention of inflammation-associated diseases, host defense peptides—particularly β-defensins—represent promising tools for maintaining livestock health and reducing the burden of infectious diseases.