title: Systemic infection of mice by wild-type but not Spv- Salmonella typhimurium is enhanced by neutralization of gamma interferon and tumor necrosis factor alpha.
abstract: The spv genes of the virulence plasmid of Salmonella typhimurium and other nontyphoidal serovars of S. enterica are involved in systemic infection by increasing the replication rate of the bacteria in host tissues beyond the intestines. We considered the possibility that the Spv virulence function is to evade suppression by the host response to infection. To examine this possibility, gamma interferon (IFN-gamma) and/or tumor necrosis factor alpha (TNF-alpha) were neutralized in BALB/c mice by intraperitoneal administration of monoclonal antibodies. Neutralization of IFN-gamma and/or TNF-alpha resulted in increased splenic infection with wild-type salmonellae after oral inoculation; however, Spv- salmonellae were defective at increasing splenic infection in cytokine-depleted mice. The use of a temperature-sensitive marker plasmid, pHSG422, indicated that neutralization of IFN-gamma caused less killing of wild-type S. typhimurium, while neutralization of TNF-alpha resulted in an increased in vivo replication rate for wild-type salmonellae. These results demonstrate that the Spv virulence function is not to evade suppression of bacterial infection normally mediated by IFN-gamma or TNF-alpha.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Florida College of Medicine, Gainesville 32610-0266, USA. gulig@college.med.ufl.edu
authors.forename: P A
authors.initials: PA
authors.lastname: Gulig
authors.forename: T J
authors.initials: TJ
authors.lastname: Doyle
authors.forename: M J
authors.initials: MJ
authors.lastname: Clare-Salzler
authors.forename: R L
authors.initials: RL
authors.lastname: Maiese
authors.forename: H
authors.initials: H
authors.lastname: Matsui
mesh_terms: D000818:Animals; D005798:Genes, Bacterial; D007371:Interferon-gamma / Q000037:antagonists & inhibitors / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D012481:Salmonella Infections, Animal / Q000276:immunology*; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000276:immunology*; D014774:Virulence / Q000235:genetics / Q000276:immunology
chemical_list: D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma