Trained Immunity Enhanced the Defense Function of Intestinal Epithelial Cells Upon Rechallenge

The complexity of pathogens poses a big challenge to the prevention of intestinal infection. Here, we reported that early LPS injection alleviated intestinal damage in mice challenged with Salmonella typhimurium, and enhanced the expression of antibacterial substances in jejunum, suggesting that the intestinal epithelial cells (IECs) could be trained, and the results of in vivo pre-stimulation then in vitro restimulation tests confirmed this. Then the independent establishment of immune memory in IECs was investigated. After comprehensively confirming that immune memory could also be established in Caco-2 cells, we used it as the IEC model and proved that the acquisition of immune memory in IECs was involved in the classic epigenetic mechanism of trained immunity. The ability of IECs to acquire trained immunity further demonstrated the potential of training the nonspecific immune responses in preventing intestinal infections. This study may provide a new strategy for effective prevention of complex intestinal pathogens.