Neuropeptide Y Boosts Intestinal Mucosal Immunity of Tilapia Infected with Streptococcus agalactiae by Reducing Inflammation and Oxidative Stress

Neuropeptides and their corresponding receptors have been observed to play a significant role in modulating immune cell functions and epithelial barrier functions. In teleost, Neuropeptide Y (NPY) is identified to be involved in the immune regulation of intestinal tissues during bacterial infections. However, the mechanism of NPY on infected gastrointestinal tissue remains unclear, as does whether other members of the NPY family, like ligand PYYb and some receptors Y7 and Y8b, also contribute to this immunoregulatory process. Herein, the responses of PYYb and receptors Y7 and Y8b were explored after pathogen challenging, as well as the effect of NPY on the gastrointestinal tissues of Nile tilapia (<i>Oreochromis niloticus</i>). Using a NPY and <i>S. agalactiae</i> co-injection model, we measured the expression of <i>pyyb</i>, <i>y7</i>, and <i>y8b</i> and the inflammatory and oxidative stress responses in gastrointestinal tissues. <i>S. agalactiae</i> infection significantly upregulated <i>pyyb</i> expression, while co-treatment with NPY further amplified its expression. Infection caused an imbalance between <i>y7</i> and <i>y8b</i> and was alleviated by NPY. Moreover, NPY contributed to immune protection. NPY co-treatment reduced inflammatory cytokine expression in the gastrointestinal tissues and alleviated tissue damage inflicted by <i>S. agalactiae</i>. Additionally, NPY mitigated immune and oxidative stress by enhancing lysozyme, AKP and ACP activities, normalizing glucose and albumin levels, and reducing lipid peroxidation (MDA). These findings demonstrated that PYYb and receptors Y7 and Y8b were involved in the immune response caused by <i>S. agalactiae</i>. NPY not only enhanced their reactions but also reduced inflammation and oxidative stress induced by the pathogen, indicating its potential as a therapeutic intervention for <i>S. agalactiae</i> infections in fish.