Porcine β-defensin 5 (pBD-5) modulates the inflammatory and metabolic host intestinal response to infection

Swine dysentery (SD) presents considerable challenges to both animal welfare and pork industry sustainability. Control and prevention of SD rely on antibiotics and non-vaccine biosecurity practices. Host defense peptides (HDPs) have emerged as promising alternatives to treat and prevent such health concern. This study investigated the effects of porcine β-defensin 5 (pBD-5) and its potential host cytotoxicity, metabolic influence, gene expression modulation and direct antimicrobial activity on Brachyspira hyodysenteriae growth in vitro. pBD-5 does not directly inhibit B. hyodysenteriae growth or significantly alters the metabolic activity or membrane integrity of host cells, indicating no significant cytotoxicity at the tested concentrations. Host transcriptome sequencing revealed a reduction in the number of differentially expressed genes in cells exposed to B. hyodysenteriae following pBD-5 treatment, when compared to the pathogen alone, suggesting an immunomodulatory effect. Pathway analysis revealed the downregulation of immune-related pathways, including IL-17, toll-like receptor (TLR), and NOD-like receptor signalling pathways, upon pBD-5 exposure. Conversely, metabolic pathways such as ribosome, protein digestion and absorption, and renin-angiotensin system were upregulated by pBD-5 treatment, hinting at a role in producing and conserving energy during the challenge. While this study offers insights into the immunomodulatory effects of pBD-5, further research is necessary to elucidate its precise mechanisms and potential applications as an alternative treatment for infectious diseases.