Interleukin-17 is a critical mediator of vaccine-induced reduction of Helicobacter infection in the mouse model.
OBJECTIVE
Despite the proven ability of immunization to reduce Helicobacter infection in mouse models, the precise mechanism of protection has remained elusive. This study explores the possibility that interleukin (IL)-17 plays a role in the reduction of Helicobacter infection following vaccination of wild-type animals or in spontaneous reduction of bacterial infection in IL-10-deficient mice.


METHODS
In mice, reducing Helicobacter infection, the levels and source of IL-17 were determined and the role of IL-17 in reduction of Helicobacter infection was probed by neutralizing antibodies.


RESULTS
Gastric IL-17 levels were strongly increased in mice mucosally immunized with urease plus cholera toxin and challenged with Helicobacter felis as compared with controls (654 +/- 455 and 34 +/- 84 relative units for IL-17 messenger RNA expression [P < .01] and 6.9 +/- 8.4 and 0.02 +/- 0.04 pg for IL-17 protein concentration [P < .01], respectively). Flow cytometry analysis showed that a peak of CD4(+)IL-17(+) T cells infiltrating the gastric mucosa occurred in immunized mice in contrast to control mice (4.7% +/- 0.3% and 1.4% +/- 0.3% [P < .01], respectively). Gastric mucosa-infiltrating CD4(+)IL-17(+) T cells were also observed in IL-10-deficient mice that spontaneously reduced H felis infection (4.3% +/- 2.3% and 2% +/- 0.6% [P < .01], for infected and noninfected IL-10-deficient mice, respectively). In wild-type immunized mice, intraperitoneal injection of anti-IL-17 antibodies significantly inhibited inflammation and the reduction of Helicobacter infection in comparison with control antibodies (1 of 12 mice vs 9 of 12 mice reduced Helicobacter infection [P < .01], respectively).


CONCLUSIONS
IL-17 plays a critical role in the immunization-induced reduction of Helicobacter infection from the gastric mucosa.
Velin
Dominique
D
Division of Gastroenterology and Hepatology, Centre Hospitalier Universitaire Vaudois and University of Lausanne, Lausanne, Switzerland. dominique.velin@chuv.ch
Favre
Laurent
L
Bernasconi
Eric
E
Bachmann
Daniel
D
Pythoud
Catherine
C
Saiji
Essia
E
Bouzourene
Hanifa
H
Michetti
Pierre
P
D000818:Animals; D001428:Bacterial Vaccines / Q000494:pharmacology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D016480:Helicobacter pylori / Q000276:immunology*; D007150:Immunohistochemistry; D007156:Immunologic Memory / Q000502:physiology*; D016753:Interleukin-10 / Q000172:deficiency / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009195:Peroxidase / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011336:Probability; D011897:Random Allocation; D012680:Sensitivity and Specificity; D018709:Statistics, Nonparametric; D018417:Th1 Cells / Q000276:immunology
D001428:Bacterial Vaccines; D016207:Cytokines; D020381:Interleukin-17; D016753:Interleukin-10; D009195:Peroxidase