Leptin receptor signaling is required for vaccine-induced protection against Helicobacter pylori.

A vaccine against Helicobacter pylori would be a desirable alternative to antibiotic therapy. Vaccination has been shown to be effective in animal models but the mechanism of protection is poorly understood. Previous studies investigating the gene expression in stomachs of vaccinated mice showed changes in adipokine expression correlated to a protective response. In this study, we investigate a well-characterized adipokine-leptin, and reveal an important role for leptin receptor signaling in vaccine-induced protection. Leptin receptor signaling-deficient (C57BL/Ks Lepr(db)), wild-type C57BL/Ks m littermates and C57BL/6 mice were vaccinated, and then challenged with H. pylori. Levels of bacterial colonization, antibody levels, and gastric infiltrates were compared. The local gene expression pattern in the stomach of leptin receptor signaling-deficient and wild-type mice was also compared using microarrays. Interestingly, while vaccinated wild-type lean C57BL/6 and C57BL/Ks m mice were able to significantly reduce colonization compared to controls, vaccinated obese C57BL/Ks Lepr(db) were not. All mice responded to vaccination, i.e. developed infiltrates predominantly of T lymphocytes in the gastric mucosa, and made H. pylori-specific antibodies. A comparison of expression profiles in protected C57BL/6 and nonprotected C57BL/Ks Lepr(db) mice revealed a subset of inflammation-related genes that were more strongly expressed in nonprotected mice. Our data suggest that functional leptin receptor signaling is required for mediating an effective protective response against H. pylori.