Host immunological conditions that determine status of Helicobacter pylori as a pathogenic or commensal bacterium

Wendelsdorf, K., A. Carbo, S. Hoops, R. Hontecillas, and J. Bassaganya-Riera, (2011) Host immunological conditions that determine status of Helicobacter pylori as a pathogenic or commensal bacterium, AAI Annual Meeting, San Francisco, CA.

In most cases H. pylori infection is asymptomatic. However, in a minority of individuals it is associated with atrophic gastritis or ulcers through an unknown mechanism. This immunopathogenesis is believed to arise from strain-specific immunomodulatory capabilities observed in vitro. To test the hypothetical role of these capabilities we have created a mathematical model of immune cells of the gastric mucosa and their response to H. pylori. A preliminary local sensitivity analysis indicates that, in typical hosts, strains that are asymptomatically tolerated are those that demonstrate the ability to invade the mucous layer as well as those that inhibit the ability of epithelial cells to secrete defensin and chemoattractants. Less intuitive results indicate that tolerated persistence is also upheld by a strain’s ability to induce secretion of inflammatory cytokines in these same epithelial cells. However, those that induce a tolerogenic response in APCs or induce cytoskeletal changes in epithelial cells are likely to elicit a tissue-damaging inflammatory response. A global sensitivity analysis revealed that each of these capabilities may have opposite effects in combination and in a context of different host immunological set points.