Leptin And IL-17 Mediated Responses In Vaccination Against <em>Helicobacter pylori</em>. — ASN Events
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  2. Poster Session 2
  3. Leptin And IL-17 Mediated Responses In Vaccination Against Helicobacter pylori.

Leptin And IL-17 Mediated Responses In Vaccination Against Helicobacter pylori. (#194)

Dorit Becher 1 2 , Jacinta Ortega 3 , Sukanya Raghavan 4 , Louise Sjökvist Ottsjo 4 , Odilia Wijburg 1 , Richard Strugnell 1 , Anna K Walduck 3
  1. Microbiology and Immunology, University of Melbourne, Melbourne, Victoria, Australia
  2. Current address, GSK Ltd, Melbourne, Victoria, Australia
  3. Biosciences Discipline, RMIT University, Melbourne, Victoria, Australia
  4. Microbiology and Immunology, University of Gothenburg, Gothenburg, Sweden

Infection with Helicobacter pylori causes chronic inflammation and damage to the gastric epithelium. This leads to chronic gastritis, and in a proportion of patients, ulcer, or gastric cancer. Candidate H. pylori vaccines tested in volunteers to date have proved poorly immunogenic and/ or to induce adverse reactions. Indeed there is some evidence that “post immunisation gastritis” occurs because the tightly controlled inflammatory response in the gastric mucosa is unbalanced1.

Vaccination is effective in animal models, and CD4+ T cells, and both the adipokine leptin (Ob)2 and interleukin 17 (IL-17)3 have been show to be essential for vaccine-induced protection against H. pylori. Leptin is pro-inflammatory, and impacts CD4+ T cell, regulatory CD4+ T cell (Treg), and even neutrophil function. IL-17 promotes neutrophil recruitment into tissues, and inflammatory cytokine production by macrophages.

Aims: To investigate the roles of leptin receptor (ObR) signalling and IL-17 in the vaccine- induced immune responses against H. pylori.

Methods: We studied responses in vaccinated wild-type C57BL/6 and ObR-signalling deficient C57BL/6 CgObR db/db mice (db/db).

Results: Vaccinated db/db mice are not protected from H. pylori challenge, we find also that gastric IL-17 production was reduced in these mice. In the stomachs of wild-type mice, both leptin and ObR are expressed on epithelial, CD4+ T cells, CD4+ Treg,, macrophages and neutrophils. Further, bone marrow chimaera studies revealed that functional ObR on BM-derived cells was essential for vaccine- induced protection. Notably, Th17 cells in the gastric mucosa of vaccinated, protected WT mice also secrete leptin.

Conclusions: Our data support a link between leptin and Th-17 responses in gastric inflammation. We hypothesise that T-cell derived leptin impacts both Treg function and IL-17 production, regulating protective responses in the vaccinated stomach.

  1. Walduck, A. K. & Becher, D. Leptin, CD4+ Treg and the prospects for vaccination against H. pylori infection. Frontiers in Immunology 3, 1–8 (2012).
  2. Wehrens, A., Aebischer, T., Meyer, T. F. & Walduck, A. K. Leptin receptor signaling is required for vaccine-induced protection against Helicobacter pylori. Helicobacter 13, 94–102 (2008)
  3. Flach, C.-F., Östberg, A. K., Nilsson, A.-T., Malefyt, R. D. W. & Raghavan, S. Proinflammatory cytokine gene expression in the stomach correlates with vaccine-induced protection against Helicobacter pylori infection in mice: an important role for interleukin-17 during the effector phase. Infect Immun 79, 879–886 (2011).