期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 192, 期 2, 页码 237-247出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.192.2.237
关键词
Salmonella; virulence; innate immunity; oxidative; nitrosative
资金
- NIAID NIH HHS [AI110181, AI44486, AI39557] Funding Source: Medline
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. typhimurim 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.
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