Eradication of Helicobacter pylori and resolution of gastritis in the gastric mucosa of IL-10-deficient mice.
BACKGROUND
Helicobacter pylori has been shown to induce pronounced gastric inflammation in the absence of interleukin-10 (IL-10) by 6 weeks post inoculation. The ability of IL-10(-/-) mice to eradicate H. pylori has not been demonstrated, possibly due to early sacrifice. Therefore, the long-term effect of enhanced gastritis on H. pylori colonization was determined in IL-10(-/-) mice.


METHODS
C57BL/6 and IL-10(-/-) mice were infected with H. pylori and assessed for the degree of gastritis, bacterial load, and in vitro T-cell recall response at 4 and 16 weeks of infection.


RESULTS
Infection of IL-10(-/-) mice resulted in significantly more severe gastritis than wild-type control mice and eradication of H. pylori by 4 weeks post inoculation. By 16 weeks, the level of gastritis in IL-10(-/-) was reduced to the levels observed in wild-type mice. Splenocytes from IL-10(-/-) mice were prone to produce significantly greater amounts of IFN-gamma than wild-type mice when stimulated with bacterial antigens.


CONCLUSIONS
These results indicate that the host is capable of spontaneously eradicating H. pylori from the gastric mucosa when inflammation is elevated beyond the chronic inflammation induced in wild-type mice, and that the gastritis dissipates following bacterial eradication. Additionally, these data provide support for a model of gastrointestinal immunity in which naturally occurring IL-10-producing regulatory T cells modulate the host response to gastrointestinal bacteria.
Matsumoto
Yuko
Y
Department of Pediatrics, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Blanchard
Thomas G
TG
Drakes
Maureen L
ML
Basu
Malini
M
Redline
Raymond W
RW
Levine
Alan D
AD
Czinn
Steven J
SJ
D000818:Animals; D000907:Antibodies, Bacterial / Q000097:blood; D005753:Gastric Mucosa / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D005756:Gastritis / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori / Q000276:immunology / Q000502:physiology*; D006801:Humans; D007113:Immunity, Innate; D007371:Interferon-gamma / Q000096:biosynthesis; D016753:Interleukin-10 / Q000172:deficiency* / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000907:Antibodies, Bacterial; D016753:Interleukin-10; D007371:Interferon-gamma