It is difficult to determine whether an immune response or target cell depletion by the infectious agent is most responsible for the control of acute primary infection. Both mechanisms can explain the basic dynamics of an acute infection—exponential growth of the pathogen followed by control and clearance—and can also be represented by many different differential equation models. Consequently, traditional model comparison techniques using time series data can be ambiguous or inconclusive. We propose that varying the inoculum dose and measuring the subsequent infectious load can rule out target cell depletion by the pathogen as the main control mechanism. Infectious load can be any measure that is proportional to the number of infected cells, such as viraemia. We show that a twofold or greater change in infectious load is unlikely when target cell depletion controls infection, regardless of the model details. Analyzing previously published data from mice infected with influenza, we find the proportion of lung epithelial cells infected was 21-fold greater (95% confidence interval 14–32) in the highest dose group than in the lowest. This provides evidence in favor of an alternative to target cell depletion, such as innate immunity, in controlling influenza infections in this experimental system. Data from other experimental animal models of acute primary infection have a similar pattern.

中文翻译：

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改变接种剂量以评估病原体在控制急性病毒感染中的免疫反应和靶细胞消耗的作用

很难确定免疫反应或感染原引起的靶细胞耗竭是否对控制急性原发感染负有最大责任。这两种机制都可以解释急性感染的基本动态——病原体呈指数增长，然后是控制和清除——也可以用许多不同的微分方程模型来表示。因此，使用时间序列数据的传统模型比较技术可能不明确或不确定。我们建议改变接种剂量和测量随后的感染负荷可以排除病原体作为主要控制机制的靶细胞耗竭。感染负荷可以是与感染细胞数量成正比的任何量度，例如病毒血症。我们表明，无论模型细节如何，当靶细胞耗竭控制感染时，感染负荷不太可能发生两倍或更大的变化。分析先前公布的感染流感小鼠的数据，我们发现最高剂量组中肺上皮细胞感染的比例是最低剂量组的 21 倍（95% 置信区间 14-32）。这为在该实验系统中控制流感感染提供了支持替代靶细胞耗竭的证据，例如先天免疫。来自其他急性原发感染实验动物模型的数据也有类似的模式。我们发现，最高剂量组感染的肺上皮细胞比例是最低剂量组的 21 倍（95% 置信区间 14-32）。这为在该实验系统中控制流感感染提供了支持替代靶细胞耗竭的证据，例如先天免疫。来自其他急性原发感染实验动物模型的数据也有类似的模式。我们发现，最高剂量组感染的肺上皮细胞比例是最低剂量组的 21 倍（95% 置信区间 14-32）。这为在该实验系统中控制流感感染提供了支持替代靶细胞耗竭的证据，例如先天免疫。来自其他急性原发感染实验动物模型的数据也有类似的模式。