Introduction and objectives: Epithelial cells are the first barrier to infection. Pathogens such as Salmonella and mastitis-causing S. aureus strains can penetrate these cells and survive in the intracellular milieu. Although the cross-presentation of bacterial antigens on MHC class I has been observed in dendritic cells, the role of epithelial cells in the process is still unclear. Based on this, we aimed to verify the capacity of swine gut epithelial cells and bovine mammary epithelial cells to present bacterial antigens and stimulate cytotoxic T lymphocytes. Materials and methods: Bovine and porcine epithelial cells transiently transfected with murine MHC-I were exposed to strains of Salmonella carrying genes involved in the invasion and intracellular fate of Salmonella tagged with the peptide SIINFEKL (OVA 256-264). A murine CD8+ T lymphocyte clone (B3Z) was then brought into contact with infected epithelial cells and the release of IL2 was quantified by ELISA. Results, discussion and conclusion: We observed that swine and bovine epithelial cells have the ability to cross-present antigens derived from the degradation of bacterial proteins. The intensity of CD8+ T cells responses varied depending on the tagged bacterial factor and suggested a more efficient presentation of antigens derived of Salmonella factors involved in intracellular survival and late replication. These preliminary data indicate the role of epithelial cells in the induction of adaptive immune response and our experimental strategy might be applied to pathogens other than Salmonella. We believe that a better understanding of the mechanisms regulating the host cytotoxic response and the fate of pathogens in the intracellular niche might provide new avenues to fight persistent bacterial infections, meeting a major animal and public health concern.