ENteric Immunity SImulator: A Tool for in silico Study of Gut Immunopathologies

Clinical symptoms of gastrointestinal (GI) infections are often caused by the inflammatory response elicited to eliminate the invading microbe. Here we present ENISI, a simulator of GI immune mechanisms in response to resident commensal bacteria as well as invading pathogens and the effect on host clinical symptoms. ENISI is a tool for identifying treatment strategies that reduce inflammation-induced damage and, at the same time, ensure pathogen removal by allowing one to test plausibility of in vitro observed behavior as explanations for observations in vivo, propose behaviors not yet tested in vitro that could explain these tissue-level observations, and conduct low-cost, preliminary experiments of proposed interventions/ treatments. An example of such application is shown in which we simulate dysentery resulting from B. hyodysenteriae infection and identify aspects of the host immune pathways that lead to continued inflammation-induced tissue damage even after pathogen elimination.