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Interleukin-17 is a critical mediator of vaccine-induced reduction of Helicobacter infection in the mouse model.

AbstractBACKGROUND & AIMS:
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.
AuthorsDominique Velin, Laurent Favre, Eric Bernasconi, Daniel Bachmann, Catherine Pythoud, Essia Saiji, Hanifa Bouzourene, Pierre Michetti
JournalGastroenterology (Gastroenterology) Vol. 136 Issue 7 Pg. 2237-2246.e1 (Jun 2009) ISSN: 1528-0012 [Electronic] United States
PMID19272385 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Bacterial Vaccines
  • Cytokines
  • Interleukin-17
  • Interleukin-10
  • Peroxidase
Topics
  • Animals
  • Bacterial Vaccines (pharmacology)
  • Cytokines (metabolism)
  • Disease Models, Animal
  • Female
  • Flow Cytometry
  • Gastric Mucosa (immunology, metabolism, pathology)
  • Helicobacter Infections (immunology, metabolism, prevention & control)
  • Helicobacter pylori (immunology)
  • Immunohistochemistry
  • Immunologic Memory (physiology)
  • Interleukin-10 (deficiency, immunology)
  • Interleukin-17 (immunology, metabolism)
  • Mice
  • Mice, Inbred C57BL
  • Peroxidase (metabolism)
  • Polymerase Chain Reaction
  • Probability
  • Random Allocation
  • Sensitivity and Specificity
  • Statistics, Nonparametric
  • Th1 Cells (immunology)

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