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.
IEEE Trans Nanobioscience. 2012 Sep;11(3):273-88. doi: 10.1109/TNB.2012.2211891.
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.
胃肠道（GI）微生物感染的临床症状通常因炎症引起的病理而加重。确定治疗和预防这种病理的新途径是必要的，但由于肠道中相互作用的免疫途径的复杂性而变得复杂，其中效应和炎症免疫细胞受到抗炎或调节细胞的调节。在这里，我们介绍了 ENteric Immunity SImulator（ENISI）的最新进展，该模拟器模拟了 GI 免疫机制对常驻共生细菌以及入侵病原体的反应，以及对肠道损伤发展的影响。ENISI 是一种用于确定潜在治疗策略的工具，这些策略可以减少炎症引起的损伤，同时通过允许人们测试体外观察到的行为是否可以解释体内观察到的现象，提出尚未在体外测试过的行为来解释这些组织水平的观察结果，以及进行低成本的、初步的拟议干预/治疗实验，从而确保病原体的清除。我们展示了这样一个应用的例子，其中我们模拟了由短螺旋体感染引起的痢疾，并确定了宿主免疫途径的各个方面，这些方面导致即使在病原体消除后，炎症引起的组织损伤仍持续存在。
