Supporting data for "High-Resolution Computational Modeling of Immune Responses in the Gut"

Helicobacter pylori causes gastric cancer in 1-2% of cases, but is also beneficial for protection against allergies and gastroesophageal diseases. An estimated 85% of H. pylori-colonized individuals do not present any detrimental effects. To study the mechanisms promoting host tolerance to the bacterium in the gastrointestinal mucosa and systemic regulatory effects, we investigated the dynamics of immunoregulatory mechanisms triggered by H. pylori using a high-performance computing driven ENteric Immunity Simulator multiscale model. Immune responses were simulated by integrating an agent-based model, ordinary and partial differential equations.
Results: The outputs were analyzed using two sequential stages: the first used a partial rank correlation coefficient regression-based and the second employed a metamodel based global sensitivity analysis. The influential parameters screened from the first stage were selected to be varied for the second stage. The outputs from both stages were combined as a training dataset to build a spatiotemporal metamodel. The Sobol’ indices measured time-varying impact of input parameters during initiation, peak and chronic phases of infection. The study identified epithelial cell proliferation and epithelial cell death as key parameters that control infection outcomes. In-silico validation showed that colonization with H. pylori decreased with a decrease in epithelial cell proliferation, which was linked to regulatory macrophages and tolerogenic dendritic cells.
Conclusion: The hybrid model of H. pylori infection identified epithelial cell proliferation as a key factor for successful colonization of the gastric niche and highlighted the role of tolerogenic dendritic cells and regulatory macrophages in modulating the host responses and shaping infection outcomes.