Helicobacter pylori is a significant cause of chronic gastric diseases, such as ulcers and gastric cancer. The host’s natural immune response to this infection is ineffective and indeed causes many of the symptoms of the diseases associated with infection. Antibiotics are currently the mainstay of treatment for the pathogen, but there is an increasing problem of resistance globally. Therefore, it is desirable to have an effective vaccine against H. pylori. Despite encouraging results in animal models, little success has been achieved in humans however. To develop a safe and effective vaccine, a better understanding of the molecular interactions between the host’s immune system and the bacterium is required.
Inflammatory Th1/17 responses are associated with both inflammatory gastritis which does not clear infection, and vaccine- induced reductions in colonization in animal models. An influx of CD4+ T cells is correlated with vaccine- induced protection. There is also evidence that gastric hormones play a role in the inflammatory response to H. pylori infection. Here we investigated the role of serotonin, also known as 5-Hydroxytryptamine (5-HT) in the response of gastric epithelia in and in vitro and a mouse model. In an in vitro model of AGS cells, qPCR analysis showed that 5-HT receptors HTR1A, HTR1B and the pro inflammatory chemokines IL-8 and CXCL8 were all upregulated, after co culture with H. pylori for 6h. In a mouse model, only HTR2B was upregulated after 3 days, at 3 weeks post infection Mip-1, Mip-2 and HTR1A were upregulated. Further we showed that vaccinated mice secreted higher levels of 5-HT in the antrum than controls. Flow cytometry analysis revealed that the expression of HTR1A was reduced on CD4+ T cells, Neutrophils and macrophages in vaccinated compared to control mice. Together these data support a role for 5-HT signaling in the inflammatory response to H. pylori infection, and that it may play a role in the protective response in vaccinated mice.