Data from: Genotype and diet shape resistance and tolerance across distinct phases of bacterial infection

Background: Host defense against pathogenic infection is composed of resistance and tolerance. Resistance is the ability of the host to limit a pathogen burden, whereas tolerance is the ability to limit the deleterious effects of a given pathogen burden. This distinction recognizes that the fittest host does not necessarily have the most aggressive immune system, suggesting that host-pathogen co-evolution involves more than an escalating arms race between pathogen virulence factors and host antimicrobial activity. How a host balances resistance and tolerance and how this balance influences the evolution of host defense remains unanswered. In order to determine how genotype-by-diet interactions and evolutionary costs of each strategy may constrain the evolution of host defense, we measured survival, fecundity, and pathogen burden over five days in ten genotypes of Drosophila melanogaster reared on two diets and infected with the Gram-negative bacterial pathogen Providencia rettgeri. Results: We demonstrated two distinct phases of infection: an acute phase that consists of high mortality, low fecundity, and high pathogen loads, and a chronic phase where there was a substantial but stable pathogen load and mortality and fecundity returned to uninfected levels. We demonstrated genetic variation for resistance in both phases of infection, but found genetic variation for tolerance only in the acute phase. We found genotype-by-diet interactions for tolerance, especially in the acute phase, but genotype-by-diet interaction did not significantly shape resistance. We found a diet-dependent positive relationship between resistance and tolerance and a weak evolutionary cost of resistance, but did not detect any costs of tolerance. Conclusions: Existing models of tolerance and resistance are overly simplistic. Multi-phase infections such as that studied here are rarely considered, but we show important differences in determination and evolutionary constraints on tolerance and resistance over the two phases of infection. Our observation of genetic variation for tolerance is inconsistent with simple models that predict evolutionary fixation of tolerance alleles, and instead indicate that genetic variation for resistance and tolerance is likely to be maintained by non-independence between resistance and tolerance, condition-dependent evolutionary costs, and environmental heterogeneity.

研究背景：宿主对抗病原体感染的宿主防御（host defense）由抗性（resistance）与耐受性（tolerance）共同组成。其中，抗性指宿主限制病原体载量的能力，而耐受性则指宿主在既定病原体载量下减轻感染有害影响的能力。该区分明确了适应性最优的宿主未必配备最为激进的免疫系统，这提示宿主-病原体协同进化的内涵，远不止病原体毒力因子与宿主抗菌活性之间的升级式军备竞赛。目前，宿主如何平衡抗性与耐受性、以及该平衡如何影响宿主防御的进化，这两个核心问题仍未得到解答。为探明基因型-饮食交互作用（genotype-by-diet interactions）与两种策略各自的进化成本（evolutionary costs）如何制约宿主防御的进化进程，我们以10个黑腹果蝇（Drosophila melanogaster）基因型为研究对象，将其饲养于两种日粮中，并以革兰氏阴性病原菌雷氏普罗威登斯菌（Providencia rettgeri）进行感染，随后在5天内监测宿主的存活率、繁殖力与病原体载量。

研究结果：本研究揭示了感染过程的两个截然不同的阶段：急性阶段以高死亡率、低繁殖力与高病原体载量为典型特征；慢性阶段则表现为病原体载量维持在较高但稳定的水平，宿主的死亡率与繁殖力恢复至未感染状态。我们在感染的两个阶段中均检测到抗性的遗传变异，但仅在急性阶段发现了耐受性的遗传变异。我们观察到耐受性存在显著的基因型-饮食交互作用，尤以急性阶段为甚，而抗性则未受该交互作用的显著调控。研究发现，抗性与耐受性之间存在饮食依赖的正相关关系，且抗性存在微弱的进化成本，但未检测到耐受性的任何进化成本。

研究结论：现有关于耐受性与抗性的进化模型过于简化。此类多阶段感染在以往研究中鲜有被纳入考量，但本研究表明，在感染的两个阶段中，耐受性与抗性的决定机制及进化约束存在显著差异。我们观测到的耐受性遗传变异，与预测耐受性等位基因会在进化中被固定的简单模型相悖；相反，抗性与耐受性之间的非独立性、依赖于环境的进化成本，以及环境异质性，很可能共同维持了抗性与耐受性的遗传变异。