p53 regulates early mucosal immunity via antigen presentation in zebrafish intestine post-SVCV vaccination

As the earliest vertebrates with innate and adaptive immunity, teleosts offer insights into the mammalian immune system. The intestine is the largest mucosal surface in the vertebrates and is a key immunological barrier contact with the external environment such as food, pathogens, and vaccine antigens. However, intestinal early immune responses post-vaccination remains unclear. This study aimed to explore intestinal vaccine uptake and early immune response mechanisms triggered by immunization. In this study, we utilized zebrafish as a model for immersion immunization. We employed zebrafish as a model for immersion immunization. We immunized zebrafish by soaking them in a vaccine for 6 h, then transferred them to normal water for continued cultivation. We observed the uptake and absorption of the vaccine by the intestines after immunization through in vivo imaging and immunofluorescence. Additionally, transcriptomic analysis was conducted to identify the key signaling pathways and gene expression changes associated with the intestinal immune response. With the increase in immunization time, a significantly enhanced fluorescent signal can be observed in the intestine. The expression level of IgZ in the intestine was nearly 4 times that of the control group at 3 days post-vaccination (dpv), and the survival rate after challenge could reach 27.91%, which was significantly higher than that of the control group. Transcriptomic analysis revealed substantial upregulation of pathways involved in the p53 signaling pathway, antigen presentation, and T cell immune regulation post-vaccination. There is a marked reduction in the proportions of CD4+ and CD8α+ T lymphocytes within the intestine of p53 mutant zebrafish. Our research disclosed that p53 is involved in the early immune response by regulating antigen presentation and induces T-cell immune responses. This investigation provides novel insights and establishes a foundational understanding of early intestinal immune responses.