Data from: The double-edged sword of immune defence and damage control: do food availability and immune challenge alter the balance?

1.Animal immune systems must adaptively balance aggressive immune resistance (ability to destroy pathogens) with infection tolerance (ability to withstand the negative effects of infection; e.g., immunopathology or damage due to pathogen metabolism).
2.Insects offer unique insight into this balancing act because phenoloxidase (PO)-mediated melanisation is a key feature of immune resistance, but PO activation obligates the production of non-specific reactive species that can cause self-damage. The antioxidant glutathione (GSH) can provide protection against such reactive molecules, but high levels of GSH can impair melanisation. In support of the hypothesis that GSH can protect insects (e.g., crickets) from self-damage during an immune response, we found that bacterially infected crickets showed a significant positive relationship between GSH haemolymph concentration and fecundity after controlling for bacterial growth rate. That is, GSH may be a mechanism of infection tolerance because it correlated with fecundity despite bacterial proliferation.
3.Next, we factorially manipulated food availability and immune activation in female crickets to examine whether the relative balance between a component of immune resistance (i.e., PO) and protection from self-damage (i.e., GSH) was plastic and sensitive to environmental conditions.
4.Glutathione and PO were positively correlated, and the PO:GSH ratio was robust and not affected by food availability or immune activation. Thus, increased investment in a mechanism of immune resistance may obligate a concomitant increase in GSH to reduce self-damage (i.e., increase infection tolerance). Chronic immune activation led to greater tolerance of oxidative stress suggesting that repeated immune activation up-regulates infection tolerance mechanisms. Food limitation led to reduced PO activity, but not GSH concentration. This result suggests that mechanisms of immune resistance may be more sensitive to resource scarcity than mechanisms of infection tolerance.
5.We demonstrate that some mechanisms of immune resistance and infection tolerance can be correlated, and that they can be affected by food availability or immune activation.

1. 动物免疫系统必须在适应性层面，在强效免疫抗性（immune resistance，即破坏病原体的能力）与感染耐受（infection tolerance，即抵御感染负面效应的能力，例如免疫病理损伤或病原体代谢引发的组织损伤）之间维持动态平衡。
2. 昆虫为探究这一平衡机制提供了独特视角：酚氧化酶（phenoloxidase, PO）介导的黑化反应是免疫抗性（immune resistance）的核心特征，但PO的激活必然诱导产生可引发自身损伤的非特异性活性物质。抗氧化剂谷胱甘肽（glutathione, GSH）可对这类活性分子起到防护作用，但过高浓度的GSH会抑制黑化反应。为验证GSH可在免疫应答（immune response）期间保护昆虫（如蟋蟀）免受自身损伤这一假说，本研究在控制细菌生长速率（bacterial growth rate）的前提下发现，被细菌感染的蟋蟀，其血淋巴（haemolymph）中GSH浓度与繁殖力（fecundity）之间存在显著正相关关系。换言之，尽管细菌发生增殖（bacterial proliferation），GSH浓度仍与繁殖力呈正相关，这表明GSH或可作为感染耐受的作用机制。
3. 本研究采用析因设计，对雌性蟋蟀的食物可获得性（food availability）与免疫激活（immune activation）状态进行操控，以此探究免疫抗性组分（即PO）与自身损伤防护机制（即GSH）之间的相对平衡是否具有可塑性，且是否会受环境条件的影响。
4. 谷胱甘肽与PO呈正相关，且PO:GSH比值较为稳健，不受食物可获得性或免疫激活状态的影响。由此可见，增加免疫抗性机制的投入，必然需要同步提升GSH的表达以降低自身损伤（即增强感染耐受能力）。长期免疫激活（chronic immune activation）可提升机体对氧化应激（oxidative stress）的耐受能力，这表明反复的免疫激活会上调感染耐受相关机制。食物限制（food limitation）会降低PO活性，但不会改变GSH浓度。该结果提示，免疫抗性机制相较于感染耐受机制，对资源匮乏（resource scarcity）的敏感性更高。
5. 本研究证实，部分免疫抗性与感染耐受机制之间存在相关性，且这些机制会受食物可获得性或免疫激活状态的影响。