Vitamin D3 activates the innate immune response and xenophagy against Nocardia seriolae through the VD receptor in liver of largemouth bass (Micropterus salmoides)

Nocardia seriolae is a pathogenic bacterium that commonly infects largemouth bass (Micropterus salmoides), causing chronic wasting disease characterized by multiple nodules. The mechanism by which Vitamin D3 (VD3) can resist Nocardia seriolae (N. seriolae)infection is unknown, although VD3 has been found to regulate innate immune response and xenophagy in mammals. Therefore, we investigated the effects of VD3 on the immune response and xenophagy of largemouth bass after N. seriolae challenge. The results demonstrate that increasing dietary VD3 intake can alleviate focal necrosis of liver cells, increase mRNA and protein levels of innate immune response-related genes, such as cGAS, STING1, TBK1, IRF3, and IFNα, decrease the content of liver autophagosomes, and increase the content of liver autophagolysosomes. Additionally, VD3 can increase mRNA expression and protein levels of genes related to liver autophagosome-lysosome fusion, including ATG16L1, ATPV0Ca, ATPV0Cb, ATPV1D, LAMP2, STX17, and VAMP8, as well as VDR. These findings suggest that VD3 contributes to the resistance of largemouth bass to N. seriolae infection by activating innate immune response and xenophagy through VDR-mediated immunomodulation.