title: Novel virulence properties of the Salmonella typhimurium virulence-associated plasmid: immune suppression and stimulation of splenomegaly.
abstract: Mice infected subcutaneously with wild-type Salmonella typhimurium, SR11, developed a significant splenomegaly when compared with mice infected with an equal number of a plasmid-cured strain. Further, the bacterial load in the spleen at 14 days after infection, measured as colony-forming units per gram tissue, was significantly higher in mice infected with the parent strain than in mice infected with the plasmid-cured strain. These data confirm the previously reported plasmid-associated ability of Salmonella to multiply within the spleen. In addition, lymph node cells (LNC) from mice infected with the parent strain had a significantly reduced ability to proliferate in response to concanavalin A, a T-cell mitogen, and to heat-killed S. typhimurium cells when compared with LNC isolated from mice infected with the plasmid-cured strain. Finally, reintroduction of a functional Tn5-tagged 90-kb plasmid into a plasmid-free strain restored its capacity to cause a marked splenomegaly and to suppress lymph node cell proliferation in BALB/c mice. These data demonstrate that the 90-kb plasmid of highly virulent S. typhimurium strains mediates several novel pathogenic properties in infected mice: (1) enhancement of the ability of Salmonella to multiply within the spleen; (2) stimulation of a splenic inflammatory response as displayed by marked splenomegaly; and (3) a general suppression of lymphocyte responsiveness to both T-cell mitogens and specific Salmonella antigens.
authors.affiliation: Department of Microbiology and Immunology, School of Medicine, College of Science and Mathematics, Wright State University, Dayton, Ohio 45431.
authors.forename: B E
authors.initials: BE
authors.lastname: Hoertt
authors.forename: J
authors.initials: J
authors.lastname: Ou
authors.forename: D J
authors.initials: DJ
authors.lastname: Kopecko
authors.forename: L S
authors.initials: LS
authors.lastname: Baron
authors.forename: R L
authors.initials: RL
authors.lastname: Warren
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D004251:DNA Transposable Elements; D005260:Female; D007165:Immunosuppression Therapy; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D010957:Plasmids; D012480:Salmonella Infections / Q000276:immunology* / Q000473:pathology; D012486:Salmonella typhimurium / Q000235:genetics / Q000472:pathogenicity*; D013163:Splenomegaly / Q000276:immunology / Q000382:microbiology*; D014774:Virulence
chemical_list: D004251:DNA Transposable Elements