title: ENteric Immunity SImulator: a tool for in silico study of gastroenteric infections.
abstract: Clinical symptoms of microbial infection of the gastrointestinal (GI) tract are often exacerbated by inflammation induced pathology. Identifying novel avenues for treating and preventing such pathologies is necessary and complicated by the complexity of interacting immune pathways in the gut, where effector and inflammatory immune cells are regulated by anti-inflammatory or regulatory cells. Here we present new advances in the development of the ENteric Immunity SImulator (ENISI), a simulator of GI immune mechanisms in response to resident commensal bacteria as well as invading pathogens and the effect on the development of intestinal lesions. ENISI is a tool for identifying potential 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 Brachyispira hyodysenteriae infection and identify aspects of the host immune pathways that lead to continued inflammation-induced tissue damage even after pathogen elimination.
authors.affiliation: Network Dynamics and Simulation Science Laboratory, and Center for Modeling Immunity to Enteric Pathogens, Virginia Bioinformatics Institute, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA. wkath83@vbi.vt.edu
authors.forename: Katherine V
authors.initials: KV
authors.lastname: Wendelsdorf
authors.forename: Maksudul
authors.initials: M
authors.lastname: Alam
authors.forename: Josep
authors.initials: J
authors.lastname: Bassaganya-Riera
authors.forename: Keith
authors.initials: K
authors.lastname: Bisset
authors.forename: Stephen
authors.initials: S
authors.lastname: Eubank
authors.forename: Raquel
authors.initials: R
authors.lastname: Hontecillas
authors.forename: Stefan
authors.initials: S
authors.lastname: Hoops
authors.forename: Madhav
authors.initials: M
authors.lastname: Marathe
mesh_terms: D000818:Animals; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D003713:Dendritic Cells / Q000276:immunology; D004403:Dysentery / Q000276:immunology / Q000382:microbiology; D004847:Epithelial Cells / Q000276:immunology; D005767:Gastrointestinal Diseases / Q000276:immunology* / Q000382:microbiology*; D041981:Gastrointestinal Tract / Q000276:immunology / Q000382:microbiology; D054884:Host-Pathogen Interactions / Q000276:immunology*; D018928:Immunity, Mucosal / Q000276:immunology; D008954:Models, Biological; D013552:Swine; D013601:T-Lymphocytes / Q000276:immunology