Dynamically linking influenza virus infection kinetics, lung injury, inflammation, and disease severity.
Dynamically linking influenza virus infection kinetics, lung injury, inflammation, and disease severity.
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动态连接流感病毒感染动力学，肺损伤，炎症和疾病严重程度。
DOI：
10.7554/elife.68864
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发表时间：
2021-07-20
期刊：
影响因子：
7.7
通讯作者：
Smith AM
中科院分区：
文献类型：
--
作者：
Myers MA;Smith AP;Lane LC;Moquin DJ;Aogo R;Woolard S;Thomas P;Vogel P;Smith AM
流感病毒导致大量的发病率和死亡率。了解宿主免疫控制功效以及不同因素如何影响肺损伤和疾病严重程度至关重要。我们建立并验证了病毒载量，感染细胞，CD8+ T细胞，肺损伤，炎症和疾病严重程度之间的动态联系，使用综合数学模型实验交换。我们的研究结果表明，炎症和病毒造成的肺损伤的动力学是不同的和非线性相关的疾病的严重程度，这两个病理测量可以独立预测使用模型衍生的感染细胞动力学。我们的研究结果进一步表明，相对的CD8+ T细胞动力学增加了肺部的百分比，其中CD8+ T细胞介导的清除率在2天内迅速加速超过48，000倍。这补充了我们的分析，显示先天性和适应性免疫介导的感染细胞清除的功效之间的负相关性，并且感染持续时间由CD8+ T细胞大小而不是功效驱动，并且如果CD8+ T细胞与感染细胞的比率足够低，则可以显著延长。重要病原体动力学和宿主病理学之间的这些联系增强了我们预测疾病进展、潜在并发症和治疗效果的能力。
Influenza viruses cause a significant amount of morbidity and mortality. Understanding host immune control efficacy and how different factors influence lung injury and disease severity are critical. We established and validated dynamical connections between viral loads, infected cells, CD8+ T cells, lung injury, inflammation, and disease severity using an integrative mathematical model-experiment exchange. Our results showed that the dynamics of inflammation and virus-inflicted lung injury are distinct and nonlinearly related to disease severity, and that these two pathologic measurements can be independently predicted using the model-derived infected cell dynamics. Our findings further indicated that the relative CD8+ T cell dynamics paralleled the percent of the lung that had resolved with the rate of CD8+ T cell-mediated clearance rapidly accelerating by over 48,000 times in 2 days. This complimented our analyses showing a negative correlation between the efficacy of innate and adaptive immune-mediated infected cell clearance, and that infection duration was driven by CD8+ T cell magnitude rather than efficacy and could be significantly prolonged if the ratio of CD8+ T cells to infected cells was sufficiently low. These links between important pathogen kinetics and host pathology enhance our ability to forecast disease progression, potential complications, and therapeutic efficacy.
影响因子：
4.3
作者：
Yates AJ;Van Baalen M;Antia R
通讯作者：
Antia R
DOI：
10.1186/cc5680
发表时间：
2007
期刊：
Critical care (London, England)
影响因子：
--
作者：
Sartorius A;Lu Q;Vieira S;Tonnellier M;Lenaour G;Goldstein I;Rouby JJ
通讯作者：
Rouby JJ
影响因子：
--
作者：
Parzych EM;DiMenna LJ;Latimer BP;Small JC;Kannan S;Manson B;Lasaro MO;Wherry EJ;Ertl HC
通讯作者：
Ertl HC