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Original Article |
Correspondence to: Pietro Mastroeni, Centre for Veterinary Science, University of Cambridge, Madingley Road, Cambridge CB3 OES, UK. Tel:44-1223-339868 Fax:44-1223-337610 E-mail: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
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