title: Antimicrobial actions of the NADPH phagocyte oxidase and inducible nitric oxide synthase in experimental salmonellosis. II. Effects on microbial proliferation and host survival in vivo.
abstract: The roles of the NADPH phagocyte oxidase (phox) and inducible nitric oxide synthase (iNOS) in host resistance to virulent Salmonella typhimurium were investigated in gp91phox(-/)-, iNOS(-/)-, and congenic wild-type mice. Although both gp91phox(-/)- and iNOS(-/)- mice demonstrated increased susceptibility to infection with S. typhimurium compared with wild-type mice, the kinetics of bacterial replication were dramatically different in the gp91phox(-/)- and iNOS(-/)- mouse strains. Greater bacterial numbers were present in the spleens and livers of gp91phox(-/)- mice compared with C57BL/6 controls as early as day 1 of infection, and all of the gp91phox(-/)- mice succumbed to infection within 5 d. In contrast, an increased bacterial burden was detected within reticuloendothelial organs of iNOS(-/)- mice only beyond the first week of infection. Influx of inflammatory CD11b(+) cells, granuloma formation, and serum interferon gamma levels were unimpaired in iNOS(-/)- mice, but the iNOS-deficient granulomas were unable to limit bacterial replication. The NADPH phagocye oxidase and iNOS are both required for host resistance to wild-type Salmonella, but appear to operate principally at different stages of infection.
authors.affiliation: Centre for Veterinary Science, University of Cambridge, Cambridge CB3 0ES, United Kingdom. pm274@cm.ac.uk
authors.forename: P
authors.initials: P
authors.lastname: Mastroeni
authors.forename: A
authors.initials: A
authors.lastname: Vazquez-Torres
authors.forename: F C
authors.initials: FC
authors.lastname: Fang
authors.forename: Y
authors.initials: Y
authors.lastname: Xu
authors.forename: S
authors.initials: S
authors.lastname: Khan
authors.forename: C E
authors.initials: CE
authors.lastname: Hormaeche
authors.forename: G
authors.initials: G
authors.lastname: Dougan
mesh_terms: D000818:Animals; D005434:Flow Cytometry; D007371:Interferon-gamma / Q000097:blood; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000502:physiology*; D052247:Nitric Oxide Synthase Type II; D012481:Salmonella Infections, Animal / Q000276:immunology* / Q000401:mortality / Q000473:pathology; D012486:Salmonella typhimurium / Q000502:physiology*
chemical_list: D008562:Membrane Glycoproteins; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; C056558:CYBB protein, human; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases