Modulation of mucosal effector and regulatory T cell responses by Helicobacter pylori

Carbo, A., M. Climent, K. Muite, M. Viladomiu, M. Pedragosa, I. Fonseca, M. Humedas, M. Humedas, P. Lu, W. T. Horne, R. Hontecillas, and J. Bassaganya-Riera (2011) Modulation of mucosal effector and regulatory T cell responses by Helicobacter pylori, AAI Annual Meeting, San Francisco, CA.

Helicobacter pylori is a gram-negative, microaerophilic bacterium that colonizes the gastric mucosa and a leading cause of gastritis, peptic ulcer and gastric cancer. While dysregulated immune responses contribute to H. pylori-mediated pathogenesis, its immunoregulatory mechanisms are incompletely understood. To characterize the mechanisms of immune modulation by H. pylori we have performed dose-titration and time-course studies in mice infected with H. pylori strain 26695. Our dose-titration results indicate an increase in the percentages of INF+Tbet+ Th1 cells, lymphocytic infiltration into the gastric lamina propria, and disease activity with increasing concentrations of the H. pylori infectious dose (i.e., 10⁶, 10⁸ and 10¹⁰ cfu/ml). The profiling of T cell responses in the gastric lymph nodes (GLN) over time illustrates an initial increase in CD4+INF+Tbet+ (Th1 cells) on day 7 post-infection followed by a predominant peak of CD4+IL10+ T cells and smaller but significant peak of CD4+IL17+ T cells on day 14 post-infection. In conclusion, gastric H. pylori infection in mice induced mucosal effector Th1 and Th17 responses that were paralleled by strong regulatory responses, thereby lending support to importance of characterizing effector and regulatory networks to better comprehend microbial pathogenesis at the site of infection.