Pivotal advance: exposure to LPS suppresses CD4+ T cell cytokine production in Salmonella-infected mice and exacerbates murine typhoid.
A number of studies have documented suppression of lymphocyte activation in mice infected with Salmonella. Here, we describe incomplete activation of CD4+ T cells following intravenous injection of specific peptide and LPS into Salmonella-infected mice. Although antigen-specific CD4+ T cells were activated by peptide/LPS to increase surface CD69 expression, they did not produce IL-2 or TNF-alpha. Suppression of cytokine production did not require prolonged exposure of the T cells to the Salmonella-infected environment, was not antigen specific, but was dependent upon the presence of LPS during stimulation. These data suggest that Salmonella-infected mice are exquisitely sensitive to the generation of a suppressive environment following innate immune stimulation with LPS. In agreement with this interpretation, repeated low-dose administration of LPS caused uncontrolled replication of attenuated Salmonella in vivo.
Srinivasan
Aparna
A
Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, University of Minnesota Medical School, McGuire Translational Research Facility, Minneapolis, MN 55455, USA.
McSorley
Stephen J
SJ
D019264:Adoptive Transfer; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000276:immunology; D004195:Disease Models, Animal; D008070:Lipopolysaccharides / Q000008:administration & dosage* / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008819:Mice, Nude; D012480:Salmonella Infections / Q000276:immunology; D012486:Salmonella typhimurium / Q000302:isolation & purification / Q000472:pathogenicity; D014435:Typhoid Fever / Q000276:immunology* / Q000473:pathology
D016207:Cytokines; D008070:Lipopolysaccharides