Enteric Immunity Simulator: A tool for in silico study of gut immunopathologies

Wendelsdorf, K., J. Bassaganya-Riera, K. Bisset, S. Eubank, R. Hontecillas and M. Marathe (2011) Enteric Immunity Simulator: A tool for in silico study of gut immunopathologies, AAI Annual Meeting, San Francisco, CA.

Here we present the newly developed ENteric Immunity SImulator (ENISI) that simulates the antagonistic inflammatory and regulatory immune pathways of the gut as individual immune cells interact with and respond to commensal and foreign bacteria. This tool has been used to reproduce a typical inflammatory response to foreign bacteria as well as the immunopathological effects of autoimmunity to commensal bacteria with 10⁶ individual cells. ENISI is built on an agent-based model that incorporates spatial effects and randomness of cell-cell and cell-bacteria contact, which can have a significant impact on whether a triggered inflammatory cascade is successfully regulated or spirals out of control. Preliminary simulations indicate the importance of cell density and epithelial cell-mediated recruitment in determining gut immunopathology. In addition, such representation allows emergent properties such as changes in bacterial demographics and evolution as a result of interaction with host immune cells. This tool will be useful to i) test the plausibility of in vitro observed immune cell responses as explanations for tissue-level damage, ii) propose mechanisms not yet tested in vitro that could explain tissue-level phenomenon, iii) conduct low-cost, preliminary tests of proposed interventions/ treatments for inflammatory diseases, iv) identify specific data to be gathered experimentally in order to characterize mechanisms of immune modulation in the gut.