title: Intestinal Inflammation Leads to a Long-lasting Increase in Resistance to Systemic Salmonellosis that Requires Macrophages But Not B or T Lymphocytes at the Time of Pathogen Challenge.
abstract: BACKGROUND
  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.
authors.affiliation: Department of Pediatrics, Mucosal Immunology and Biology Research Center, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Estela
authors.initials: E
authors.lastname: Trebicka
authors.forename: Nanda Kumar N
authors.initials: NK
authors.lastname: Shanmugam
authors.forename: Kejie
authors.initials: K
authors.lastname: Chen
authors.forename: Chien-Wen
authors.initials: CW
authors.lastname: Su
authors.forename: Hai Ning
authors.initials: HN
authors.lastname: Shi
authors.forename: Bobby J
authors.initials: BJ
authors.lastname: Cherayil
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D058491:Bacterial Load; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003092:Colitis / Q000139:chemically induced / Q000276:immunology* / Q000382:microbiology; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D007422:Intestines / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000382:microbiology; D012486:Salmonella typhimurium / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D016264:Dextran Sulfate