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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

Lookup NU author(s): Professor Carlos Hormaeche

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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.


Publication metadata

Author(s): Mastroeni P, Vazquez-Torres A, Fang FC, Xu Y, Khan S, Hormaeche CE, Dougan G

Publication type: Article

Publication status: Published

Journal: Journal of Experimental Medicine

Year: 2000

Volume: 192

Issue: 2

Pages: 237-247

ISSN (print): 0022-1007

ISSN (electronic): 1540-9538

Publisher: Rockefeller University Press

URL: http://dx.doi.org/10.1084/jem.192.2.237

DOI: 10.1084/jem.192.2.237

PubMed id: 10899910


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Funding

Funder referenceFunder name
AI110181NIAID NIH HHS
AI39557NIAID NIH HHS
AI44486NIAID NIH HHS
F32 AI010181NIAID NIH HHS
R01 AI044486NIAID NIH HHS
R01 AI039557NIAID NIH HHS

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