Helicobacter pylori infection in pigs is dominated by a Th1 and cytotoxic immune response

Kronsteiner, B., J. Bassaganya-Riera, C. Washington, S. Vento, M. Pedragosa, M. Viladomiu, A. Carbo and R. Hontecillas (2012) Helicobacter pylori infection in pigs is dominated by a Th1 and cytotoxic immune response, American Association of Immunologists Annual Meeting, Boston MA

H. pylori is the leading cause for peptic ulcer disease and gastric adenocarcinoma. While iTreg are required for long-term colonization without disease, Th1 and Th17 responses are associated with lower bacterial load at the expense of gastric pathology. We have developed computational models of H. pylori infection predicting a dominant Th1-response that results in lesion development in the gastric mucosa. In this study, pigs were infected with H. pylori strain SS1 or J99. Changes in PBMC populations were monitored over 2 months. Bacterial loads were assessed at 9 and 57 days post-infection. Both strains elicit a Th1 response with increased percentage of CD4+Tbet+ cells and elevated Tbet and IFN-γ mRNA in PBMC. A subset of CD8β+ cells expressing Tbet increased due to infection. These cells expressed low levels of CD8β, a property of cytotoxic T cells previously exposed to their cognate peptide. A significant increase of NK cells was observed in infected pigs pointing towards a predominant cytotoxic immune response. Strain J99 evoked a more dramatic acute response associated with bacterial clearance, while strain SS1 showed long-term colonization capacity. Ex vivo functional assays indicate strain-specific, weak and suppressed memory immune responses suggesting that specific virulence factors contribute to suppression of immune responses and chronic persistence. Data from this study will be used in the modeling process to refine computational models of H. pylori infection.