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Infection and Immunity, August 2003, p. 4733-4741, Vol. 71, No. 8
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.8.4733-4741.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Induction of Antimicrobial Pathways during Early-Phase Immune Response to Salmonella spp. in Murine Macrophages: Gamma Interferon (IFN-{gamma}) and Upregulation of IFN-{gamma} Receptor Alpha Expression Are Required for NADPH Phagocytic Oxidase gp91-Stimulated Oxidative Burst and Control of Virulent Salmonella spp.

N. Foster, S. D. Hulme, and P. A. Barrow*

Division of Environmental Microbiology, Institute for Animal Health, Compton Laboratory, Newbury, Berkshire RG20 7NN, United Kingdom

Received 4 December 2002/ Returned for modification 11 February 2003/ Accepted 1 May 2003

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.


* Corresponding author. Mailing address: Division of Environmental Microbiology, Institute for Animal Health, Compton Laboratory, Compton, Newbury, Berkshire RG20 7NN, United Kingdom. Phone: 44 1635 578411. Fax: 44 1635 577263. E-mail: paul.barrow{at}bbsrc.ac.uk.

Editor: B. B. Finlay


Infection and Immunity, August 2003, p. 4733-4741, Vol. 71, No. 8
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.8.4733-4741.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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