Agent-based modeling reveals benefits of heterogeneous and stochastic cell populations during cGAS-mediated IFNβ production
Agent-based modeling reveals benefits of heterogeneous and stochastic cell populations during cGAS-mediated IFNβ production
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DOI：
10.1093/bioinformatics/btaa969
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发表时间：
2021-05-15
期刊：
影响因子：
5.8
通讯作者：
Shoemaker, Jason E.
中科院分区：
文献类型：
--
作者：
Gregg, Robert W.;Shabnam, Fathima;Shoemaker, Jason E.
动机：cGAS通路是先天免疫系统的一个组成部分，负责检测致病性DNA和上调干扰素β (IFN β)。实验证据表明，IFN β信号发生在高度异质性的细胞中，具有随机性；然而，这些属性的好处还不清楚。为了研究随机性和异质性如何影响IFN β的产生，我们开发了一个基于agent的模型来模拟DNA转染和病毒感染。结果：我们发现异质性可以增强感染期间IFN β的反应。此外，通过改变IFN β的随机程度，我们发现只有一部分细胞（20-30%）在感染期间需要做出反应。超过这个范围对防止细胞死亡或减少病毒载量没有额外的保护作用。总的来说，这些模拟表明异质性和随机性对于调节免疫效力同时最大限度地减少感染期间的细胞死亡是重要的。
Motivation: The cGAS pathway is a component of the innate immune system responsible for the detection of pathogenic DNA and upregulation of interferon beta (IFN beta). Experimental evidence shows that IFN beta signaling occurs in highly heterogeneous cells and is stochastic in nature; however, the benefits of these attributes remain unclear. To investigate how stochasticity and heterogeneity affect IFN beta production, an agent-based model is developed to simulate both DNA transfection and viral infection.Results: We show that heterogeneity can enhance IFN beta responses during infection. Furthermore, by varying the degree of IFN beta stochasticity, we find that only a percentage of cells (20-30%) need to respond during infection. Going beyond this range provides no additional protection against cell death or reduction of viral load. Overall, these simulations suggest that heterogeneity and stochasticity are important for moderating immune potency while minimizing cell death during infection.