Infections caused by Salmonella enterica serovar Typhimurium (S. typhimurium) cause important economic problems in the swine industry and threaten the integrity of a safe and healthy food supply. Controlling the prevalence of Salmonella in pig production requires a thorough knowledge of the response processes that occurs in the gut associated immune tissues. To explore the in vivo porcine response to S. typhimurium, MLN samples from four control pigs and twelve infected animals at 1, 2 and 6 days post infection (dpi) were collected to quantify the mRNA expression of gene coding for 42 innate immune-related molecules. In addition, the presence of S. typhimurium in MLN was examined and its effect on tissue micro-anatomy. Higher S. typhimurium loads were observed at 2dpi, triggering an innate immune response, marked by a substantial infiltration of phagocytes and up-regulation of pro-inflammatory genes. Such response resulted in a significant decrease in pathogen burden in MLN at 6dpi, although Salmonella could not be completely eliminated from tissue. Furthermore, our results suggest that in porcine infections, S. typhimurium might interferes with dendritic cell-T cell interactions and this strategy could be involved in the conversion of Salmonella infected pigs to a carrier state.