| Summary: | β-Defensins are cationic antimicrobial peptides (AMPs) that play an important role in the innate immune defense of bovines. They are constitutively expressed in mammary glands and induced differently in response to pathogens. Their expression is influenced by various factors, including hormones, plant-derived compounds, and dietary energy imbalance. The toll-like receptors (TLRs)/nuclear factor-kappa B (NF-κB) pathway plays a crucial role in β-defensin induction, while alternative pathways such as mitogen-activated protein kinase (MAPK) and epigenetic regulation also make substantial contributions. β-Defensins exhibit bactericidal activity against a wide range of pathogens, including two major mastitis pathogens, <i>Escherichia coli</i> (<i>E. coli</i>) and <i>Staphylococcus aureus</i> (<i>S. aureus</i>), primarily through membrane disruption. β-Defensins have low cytotoxicity to host cells and demonstrate immunomodulatory properties, and pathogens also display minimal resistance to these AMPs. Given the increasing concern in antimicrobial resistance, the potential of β-defensins as natural antimicrobials has garnered considerable attention. This article provides an overview of the characteristics of bovine β-defensins, their expression pathways, their mode of action, and factors influencing their expression in the mammary glands of cattle. Additionally, it identifies the current gaps in research within this field and suggests areas that require further investigation. Understanding the regulation and function of β-defensins offers valuable insights to develop effective strategies for strengthening the immune system of mammary glands, reducing the reliance on synthetic antimicrobials, and explore novel natural antimicrobial alternatives.
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