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

Pietro Mastroeni, Andrés Vazquez-Torres, Ferric C. Fang, Yisheng Xu, Shahid Khan, Carlos E. Hormaeche, Gordon Dougan

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294 Citations (Scopus)

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 γ 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.

Original languageEnglish
Pages (from-to)237-247
Number of pages11
JournalJournal of Experimental Medicine
Volume192
Issue number2
DOIs
Publication statusPublished - 17 Jul 2000
Externally publishedYes

Keywords

  • Innate immunity
  • Nitrosative
  • Oxidative
  • Salmonella
  • Virulence

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