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.
- Innate immunity