Effects of Aging on Influenza Virus Infection Dynamics
Effects of Aging on Influenza Virus Infection Dynamics
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DOI：
10.1128/jvi.03644-13
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发表时间：
2014-04-01
影响因子：
5.4
通讯作者：
Meyer-Hermann, Michael
中科院分区：
文献类型：
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作者：
Hernandez-Vargas, Esteban A.;Wilk, Esther;Meyer-Hermann, Michael
65岁以上的人（老年人）感染流感病毒的后果通常更为严重。免疫衰老会增加对病毒感染的易感性，并使疫苗接种效果降低。了解免疫系统中与年龄相关的变化对于设计预防和免疫调节策略以降低老年人的发病率和死亡率至关重要。在这里，我们提出了不同的数学模型，利用年轻和老年小鼠的实验数据来定量了解流感病毒感染过程中的免疫策略。模拟结果表明，CD8(+) T 细胞对于年轻和老年小鼠的充分病毒清除动力学发挥着核心作用。添加自然杀伤细胞去除感染细胞并没有改善年轻或老年动物的模型拟合度。我们分别检查了细胞因子α/β干扰素（IFN-α/β）、IFN-γ和肿瘤坏死因子α（TNF-α）促进的细胞的抗感染状态。活化的 CD8(+) T 细胞与任何细胞因子的组合在年轻和老年动物中提供了最佳的配合。感染后3天内，老年小鼠的基本繁殖数比年轻小鼠低1.5倍（P
The consequences of influenza virus infection are generally more severe in individuals over 65 years of age (the elderly). Immunosenescence enhances the susceptibility to viral infections and renders vaccination less effective. Understanding age-related changes in the immune system is crucial in order to design prophylactic and immunomodulatory strategies to reduce morbidity and mortality in the elderly. Here, we propose different mathematical models to provide a quantitative understanding of the immune strategies in the course of influenza virus infection using experimental data from young and aged mice. Simulation results suggested a central role of CD8(+) T cells for adequate viral clearance kinetics in young and aged mice. Adding the removal of infected cells by natural killer cells did not improve the model fit in either young or aged animals. We separately examined the infection-resistant state of cells promoted by the cytokines alpha/beta interferon (IFN-alpha/beta), IFN-gamma, and tumor necrosis factor alpha (TNF-alpha). The combination of activated CD8(+) T cells with any of the cytokines provided the best fits in young and aged animals. During the first 3 days after infection, the basic reproductive number for aged mice was 1.5-fold lower than that for young mice (P