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.
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 (gp91(phox)) 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.
Foster
N
N
Division of Environmental Microbiology, Institute for Animal Health, Compton Laboratory, Newbury, Berkshire RG20 7NN, United Kingdom.
Hulme
S D
SD
Barrow
P A
PA
D000818:Animals; D002216:Captopril / Q000031:analogs & derivatives / Q000494:pharmacology; D002460:Cell Line; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007371:Interferon-gamma / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics*; D011994:Recombinant Proteins; D016897:Respiratory Burst; D012475:Salmonella / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity* / Q000502:physiology; D019779:Salmonella enterica / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D012486:Salmonella typhimurium / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity / Q000502:physiology; D015854:Up-Regulation; D014774:Virulence / Q000235:genetics; D000096743:Interferon gamma Receptor
D002216:Captopril; D006861:Hydrogen Peroxide; D007371:Interferon-gamma; D008562:Membrane Glycoproteins; D000074662:NADPH Oxidase 2; D019255:NADPH Oxidases; D017382:Reactive Oxygen Species; D017471:Receptors, Interferon; D011994:Recombinant Proteins; D000096743:Interferon gamma Receptor; C056558:CYBB protein, human