title: Salmonella typhimurium strains carrying independent mutations display similar virulence phenotypes yet are controlled by distinct host defense mechanisms.
abstract: The outcome of Salmonella infection in the mammalian host favors whoever succeeds best in disturbing the equilibrium between coordinate expression of bacterial (virulence) genes and host defense mechanisms. Intracellular persistence in host cells is critical for pathogenesis and disease, because Salmonella typhimurium strains defective in this property are avirulent. We examined whether similar host defense mechanisms are required for growth control of two S. typhimurium mutant strains. Salmonella pathogenicity island 2 (SPI2) and virulence plasmid-cured Salmonella mutants display similar virulence phenotypes in immunocompetent mice, yet their gene loci participate in independent virulence strategies. We determined the role of TNF-alpha and IFN-gamma as well as different T cell populations in infection with these Salmonella strains. After systemic infection, IFN-gamma was essential for growth restriction of plasmid-cured S. typhimurium, while SPI2 mutant infections were controlled in the absence of IFN-gamma. TNFRp55-deficiency restored systemic virulence to both Salmonella mutants. After oral inoculation, control of plasmid-cured bacteria substantially relied on both IFN-gamma and TNF-alpha signaling while control of SPI2 mutants did not. However, for both mutants, ultimate clearance of bacteria from infected mice depended on alphabeta T cells.
authors.affiliation: Department of Immunology, Max-Planck-Institut für Infektionsbiologie, Berlin, Germany. raupach@mpiib-berlin.mpg.de
authors.forename: Bärbel
authors.initials: B
authors.lastname: Raupach
authors.forename: Nicole
authors.initials: N
authors.lastname: Kurth
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfeffer
authors.forename: Stefan H E
authors.initials: SH
authors.lastname: Kaufmann
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology; D007113:Immunity, Innate / Q000235:genetics; D016867:Immunocompromised Host / Q000235:genetics; D007371:Interferon-gamma / Q000502:physiology; D007424:Intracellular Fluid / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D010641:Phenotype; D010957:Plasmids; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000502:physiology; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology; D047888:Receptors, Tumor Necrosis Factor, Type I; D012481:Salmonella Infections, Animal / Q000235:genetics / Q000276:immunology* / Q000382:microbiology*; D012486:Salmonella typhimurium / Q000235:genetics* / Q000254:growth & development / Q000276:immunology / Q000472:pathogenicity*; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology; D014774:Virulence
chemical_list: D015703:Antigens, CD; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma