基于agent的结核免疫系统动力学分析建模方法

F. Pappalardo, G. Russo, M. Pennisi, G. Sgroi, G. Palumbo, S. Motta, Epifanio Fichera
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引用次数: 5

摘要

结核病是世界上最致命的疾病之一,感染了世界上三分之一的人口,主要是在发展中国家。然而,由于世界人口流动性增加,以及出现了几种具有多重耐药性的新菌株,结核病对发达国家也再次变得非常危险。为了帮助找到新的治疗结核病的干预措施,我们提出了一个名为UISS(通用免疫系统模拟器)的计算建模基础设施的应用,该基础设施能够模拟免疫系统活动的主要特征和动态。我们展示了usis的进一步发展,以考虑潜在的结核病发病机制及其与宿主免疫系统的相互作用。尽管该模型可以利用免疫参数和遗传信息进一步个性化,但基于现有数据,我们获得了能够再现持续潜伏感染或发展为活动性疾病的模拟场景。特别是,UISS能够在细胞和分子水平上模拟结核分枝杆菌参与肺泡巨噬细胞的早期涌入和中性粒细胞的募集,直到结核性肉芽肿形成的机制。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
An agent based modeling approach for the analysis of tuberculosis – immune system dynamics
Tuberculosis is one of the world’s deadliest diseases that infects one third of the world’s population, mostly in developing countries. However, tuberculosis is becoming again very dangerous also for developed countries, due to the increased mobility of the world population, and the appearance of several new bacterial strains that are multi-drug resistant. With the aim to help in finding new therapeutic interventions against tuberculosis, we present the application of a computational modeling infrastructure named UISS (Universal Immune System Simulator) able to simulate the main features and dynamics of the immune system activities. We show a further development of UISS to consider the underlying tuberculosis pathogenesis and its interaction with the host immune system. Even though the model can be further personalized employing immunological parameters and genetic information, based on the available data, we obtained simulation scenarios able to reproduce persistent latent infection or the development of active disease. In particular, UISS is able to simulate those mechanisms in which M. tuberculosis is involved in the early influx of alveolar macrophages and recruited neutrophils until the formation of the tuberculous granuloma, at both cellular and molecular levels.
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