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Modelling within-host macrophage dynamics in influenza virus infection.
Journal of Theoretical Biology ( IF 2 ) Pub Date : 2020-09-20 , DOI: 10.1016/j.jtbi.2020.110492
Ke Li 1 , James M McCaw 2 , Pengxing Cao 1
Affiliation  

Human respiratory disease associated with influenza virus infection is of significant public health concern. Macrophages, as part of the front line of host innate cellular defence, have been shown to play an important role in controlling viral replication. However, fatal outcomes of infection, as evidenced in patients infected with highly pathogenic viral strains, are often associated with prompt activation and excessive accumulation of macrophages. Activated macrophages can produce a large amount of pro-inflammatory cytokines, which leads to severe symptoms and at times death. However, the mechanism for rapid activation and excessive accumulation of macrophages during infection remains unclear. It has been suggested that the phenomena may arise from complex interactions between macrophages and influenza virus. In this work, we develop a novel mathematical model to study the relationship between the level of macrophage activation and the level of viral load in influenza infection. Our model combines a dynamic model of viral infection, a dynamic model of macrophages and the essential interactions between the virus and macrophages. Our model predicts that the level of macrophage activation can be negatively correlated with the level of viral load when viral infectivity is sufficiently high. We further identify that temporary depletion of resting macrophages in response to viral infection is a major driver in our model for the negative relationship between the level of macrophage activation and viral load, providing new insight into the mechanisms that regulate macrophage activation. Our model serves as a framework to study the complex dynamics of virus-macrophage interactions and provides a mechanistic explanation for existing experimental observations, contributing to an enhanced understanding of the role of macrophages in influenza viral infection.



中文翻译:

在流感病毒感染中模拟宿主内巨噬细胞动力学。

与流感病毒感染有关的人类呼吸系统疾病引起了公众极大的关注。巨噬细胞作为宿主先天细胞防御的前线一部分,已显示在控制病毒复制中起重要作用。然而,如感染高致病性病毒株的患者所证明的那样,感染的致命结果通常与迅速激活和巨噬细胞过度积累有关。活化的巨噬细胞会产生大量促炎性细胞因子,从而导致严重的症状,有时甚至死亡。然而,在感染过程中快速激活和巨噬细胞过度积累的机制仍不清楚。有人认为,这种现象可能是由于巨噬细胞和流感病毒之间复杂的相互作用引起的。在这项工作中 我们开发了一种新型的数学模型来研究流感病毒感染中巨噬细胞活化水平与病毒载量水平之间的关系。我们的模型结合了病毒感染的动态模型,巨噬细胞的动态模型以及病毒和巨噬细胞之间的基本相互作用。我们的模型预测,当病毒感染性足够高时,巨噬细胞激活水平可能与病毒载量水平呈负相关。我们进一步发现,在响应巨噬细胞激活水平和病毒载量之间的负相关关系的模型中,静止巨噬细胞对病毒感染的暂时耗竭是主要驱动因素,从而为调节巨噬细胞激活的机制提供了新的见解。

更新日期:2020-09-29
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