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Induction of antimicrobial pathways during early-phase immune response to Salmonella spp. in murine macrophages: gamma interferon (IFN-g) and upregulation of IFN-gamma receptor alpha expression are required for NADPH phagocytic oxidase gp91-stimulated oxidative burst and control of virulent Salmonella spp.

Lookup NU author(s): Dr Neil Foster

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Abstract

The effect of gamma interferon (IFN-{gamma}) on elevation of reactive oxygen species and the viability of virulent wild-type and avirulent mutants of Salmonella enterica serovar Typhimurium and S. enterica serovar Infantis was studied in a murine macrophage cell line (J774.2 cells). S. enterica serovar Typhimurium 14028 phoP and a rough lipopolysaccharide mutant of S. enterica serovar Infantis 1326/28 ({phi}r) (avirulent mutants) induced NADPH phagocytic oxidase gp91 (gp91phox) activity and a significant (P < 0.05) elevation of reactive oxygen species within 12 h without coculture with IFN-{gamma}. This coincided with reduced survival of S. enterica serovar Typhimurium14028 phoP or stasis of S. enterica serovar Infantis {phi}r. Fluorometric studies indicated that expression of IFN-{gamma} on infected J774.2 cells was not significantly (P > 0.05) elevated. However, studies with the virulent S. enterica serovar Typhimurium strains showed that a comparable level of control of bacterial numbers could only be achieved by coculture with IFN-{gamma}. This coincided with significant upregulation of IFN-{gamma} receptor alpha expression on the surface of J774.2 cells and was completely abolished by N-acetyl-L-cysteine captopril (an inhibitor of reactive oxygen species). Delay in reactive oxygen species induction due to a requirement for IFN-{gamma} and upregulation of IFN-{gamma} receptor alpha in macrophages infected with virulent salmonellae may result in greater dissemination of virulent salmonellae in host tissue.


Publication metadata

Author(s): Foster N; Hulme SD; Barrow PA

Publication type: Article

Publication status: Published

Journal: Infection and Immunity

Year: 2003

Volume: 71

Issue: 8

Pages: 4733-4741

ISSN (print): 0019-9567

ISSN (electronic): 1098-5522

Publisher: American Society for Microbiology

URL: http://dx.doi.org/10.1128/IAI.71.8.4733-4741.2003

DOI: 10.1128/IAI.71.8.4733-4741.2003


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