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Original Article |
pm274{at}cm.ac.uk
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
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.
Key Words: Salmonella virulence innate immunity oxidative nitrosative
© 2000 The Rockefeller University Press
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