Data from: Nonlinear disease tolerance curves reveal distinct components of host responses to viral infection

The ability to tolerate infection is a key component of host defence and
offers potential novel therapeutic approaches for infectious diseases. To
yield successful targets for therapeutic intervention, it is important
that the analytical tools employed to measure disease tolerance are able
to capture distinct host responses to infection. Here, we show that
commonly used methods that estimate tolerance as a linear relationship
should be complemented with more flexible, nonlinear estimates of this
relationship which may reveal variation in distinct components such as
host vigour, sensitivity to increases in pathogen loads, and the severity
of the infection. To illustrate this, we measured the survival of
Drosophila melanogaster carrying either a functional or non-functional
regulator of the JAK-STAT immune pathway (G9a) when challenged with a
range of concentrations of Drosophila C virus (DCV). While classical
linear model analyses indicated that G9a affected tolerance only in
females, a more powerful nonlinear logistic model showed that G9a mediates
viral tolerance to different extents in both sexes. This analysis also
revealed that G9a acts by changing the sensitivity to increasing pathogen
burdens, but does not reduce the ultimate severity of disease. These
results indicate that fitting nonlinear models to host health–pathogen
burden relationships may offer better and more detailed estimates of
disease tolerance.

感染耐受能力是宿主防御的关键组成部分，亦为传染病的新型治疗策略提供了潜在可能。为获得可用于治疗干预的有效靶点，用于衡量疾病耐受的分析工具需能够捕捉宿主对感染的不同应答反应，这一点至关重要。本研究表明，当前常用的将耐受估算为线性关系的分析方法，需辅以更为灵活的非线性关系估算方式——此类非线性方法可揭示宿主活力、病原体负荷增加时的敏感性以及感染严重程度等不同维度的差异。为验证这一结论，我们对携带JAK-STAT免疫通路（JAK-STAT immune pathway）调控因子G9a的功能型或非功能型载体的黑腹果蝇（Drosophila melanogaster），在受到不同浓度果蝇C病毒（Drosophila C virus, DCV）侵染后的存活情况进行了检测。经典线性模型分析显示，G9a仅在雌性果蝇中对耐受产生影响；而效力更强的非线性逻辑斯蒂模型则表明，G9a在两性果蝇中以不同程度介导病毒耐受。该分析还揭示，G9a通过改变宿主对病原体负荷升高的敏感性发挥作用，但并不会降低疾病的最终严重程度。上述结果表明，将非线性模型应用于宿主健康-病原体负荷关系的拟合，或可对疾病耐受做出更精准且更细致的估算。