Severe inflammation and reduced bacteria load in murine helicobacter infection caused by lack of phagocyte oxidase activity.
The vaccine-induced immune mechanisms that protect against Helicobacter pylori infection in the mouse model have not been identified. This study investigated the contribution of reactive oxygen and nitrogen intermediates to Helicobacter pathogenesis and immunity. Mice deficient in nicotinamide-adenine dinucleotide phosphate oxidase activity (gp91(phox-/-)), nitric oxide synthase activity (NOS2(-/-)), or both (gp91(phox-/-)/NOS2(-/-)) were infected with Helicobacter organisms and evaluated for inflammation and bacteria load. Infection of all 3 transgenic strains resulted in significantly more inflammation than found in infected C57BL/6 wild-type mice. However, only gp91(phox-/-) and gp91(phox-/-)/NOS2(-/-) mice had significantly reduced numbers of infected gastric glands. Intranasal immunization of NOS2(-/-) or gp91(phox-/-)/NOS2(-/-) mice against H. pylori resulted in protective immunity comparable to that seen in C57BL/6 control mice. Therefore, reactive oxygen species may play a role in limiting the inflammatory response associated with H. pylori infection of the gastric mucosa but may also limit the host's ability to eradicate Helicobacter organisms.
Blanchard
Thomas G
TG
Department of Pediatrics, Case Western Reserve University School of Medicine, Cleveland, Ohio 44106, USA. tgb4@po.cwru.edu
Yu
Feiwen
F
Hsieh
Chen-Lung
CL
Redline
Raymond W
RW
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D017353:Gene Deletion; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology*; D016480:Helicobacter pylori / Q000276:immunology* / Q000302:isolation & purification / Q000502:physiology; D007074:Immunoglobulin G / Q000097:blood; D007249:Inflammation / Q000201:enzymology / Q000276:immunology / Q000382:microbiology; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010586:Phagocytes / Q000201:enzymology* / Q000276:immunology; D013272:Stomach Diseases / Q000276:immunology / Q000382:microbiology / Q000473:pathology; D013997:Time Factors
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D019255:NADPH Oxidases