Intestinal inflammation is associated with systemic translocation of commensal antigens and the consequent activation of B and T lymphocytes. The long-term consequences of such immune activation are not completely understood.Methods:
C57BL/6 mice were subjected to 2 courses of treatment with dextran sulfate sodium (DSS) to induce colitis. Two to 7 weeks after the DSS treatment, the mice were infected intraperitoneally with Salmonella enterica serovar Typhimurium. The outcome of infection was evaluated based on survival and tissue pathogen burden.Results:
Mice that had recovered from DSS colitis displayed a significant increase in resistance to S. Typhimurium infection as indicated by improved survival and decreased tissue pathogen numbers. The colitis-induced increase in resistance to systemic salmonellosis lasted for as long as 7 weeks after discontinuing DSS and was dependent on T lymphocytes but not on B cells. Interestingly, depletion of CD4+ and CD8+ T cells just before the Salmonella infection did not alter the colitis-induced increase in resistance. Mice that had recovered from colitis had evidence of persistent activation of resident peritoneal macrophages and enhanced Salmonella-induced neutrophil recruitment to the peritoneum. Macrophage depletion with clodronate liposomes abrogated the colitis-induced increase in resistance to Salmonella.Conclusions:
Taken together, our results indicate that DSS colitis leads to a long-lasting increase in resistance to Salmonella infection that is initiated in a T cell–dependent manner but is ultimately mediated independently of B and T cells as a result of persistent changes in innate immune cell function.