Mechanism of intestinal mucosal immunity mediated by Blimp-1 upon porcine epidemic diarrhea virus infection

Porcine epidemic diarrhea virus (PEDV) is a devastating pathogen, which can cause vomiting, diarrhea, dehydration and high morbidity and mortality among neonatal piglets. Due to rapid viral mutations, diverse strains, and delays in vaccine updates, PEDV continues to emerge frequently, inflicting substantial economic losses on the global swine industry. PEDV infection is a dynamic process characterized by viral replication in the cytoplasm of villous epithelial cells throughout the small intestine, reflecting a complex interplay between the virus and the host immune response. The intestinal tract is the largest immune organ in the body, and the gut-associated lymphoid tissue (GALT) is the key antigen sampling and immune inductive site within the intestinal wall. The GALT of human and mice distributes along the small and large intestines, such as isolated lymphoid follicles and Peyer's patches (PPs). PPs are lymphoid structures situated adjacent to the intestinal epithelium and contribute to the first line of immunological defence. There are various differentiated cell types carrying out unique and specialized functions in PPs, including B cells. These cells play a crucial role as producer of secretory IgA, the isotype that is predominantly found at mucosal sites. Our previous study showed that PEDV-induces TGF-β1 production, which inhibits IgA production and plasma cell differentiation in piglets. This is different from what was reported in mice. This highlights the need for a deeper understanding of porcine B cell development during PEDV infection. In summary, this project will focus on the development and differentiation of B cells in PPs and the villus epithelium during PEDV infection. By using single-cell RNA sequencing and in vitro co-cultures of intestinal organoids with B cells, we aim to provide a theoretical basis for the prevention, monitoring, and treatment of PEDV