Data from: Oxidant trade-offs in immunity: an experimental test in a lizard

Immune system functioning and maintenance entails costs which may limit investment into other processes such as reproduction. Yet, the proximate mechanisms and ‘currencies’ mediating the costs of immune responses remain elusive. In vertebrates, up-regulation of the innate immune system is associated with rapid phagocytic production of pro-oxidant molecules (so-called ‘oxidative burst’ responses). Oxidative burst responses are intended to eliminate pathogens but may also constitute an immunopathological risk as they may induce oxidative damage to self cells. To minimize the risk of infection and, at the same time, damage to self, oxidative burst activity must be carefully balanced. The current levels of pro- and antioxidants (i.e. the individual oxidative state) is likely to be a critical factor affecting this balance, but this has not yet been evaluated. Here, we perform an experiment on wild-caught painted dragon lizards (Ctenophorus pictus) to examine how the strength of immune-stimulated oxidative burst responses of phagocytes in whole blood relates to individual oxidative status under control conditions and during an in vivo immune challenge with Escherichia coli lipopolysaccharide (LPS). Under control conditions, oxidative burst responses were not predicted by the oxidative status of the lizards. LPS-injected individuals showed a strong increase in pro-oxidant levels and a strong decrease in antioxidant levels compared to control individuals demonstrating a shift in the pro-/antioxidant balance. Oxidative burst responses in LPS-injected lizards were positively related to post-challenge extracellular pro-oxidants (reflecting the level of cell activation) and negatively related to pre-challenge levels of mitochondrial superoxide (suggesting an immunoregulatory effect of this pro-oxidant). LPS-challenged males had higher oxidative burst responses than females, and in females oxidative burst responses seemed to depend more strongly on antioxidant status than in males. Our results confirm the idea that oxidative state may constrain the activity of the innate immune system. These constraints may have important consequences for the way selection acts on pro-oxidant generating processes.

免疫系统的功能运作与维持需要消耗资源，这可能会限制生物体对繁殖等其他生命过程的资源投入。然而，介导免疫应答成本的近因机制与核心量化指标仍不明晰。在脊椎动物中，先天免疫系统的激活会伴随吞噬细胞快速产生活性促氧化剂分子，即所谓的"氧化爆发（oxidative burst）"应答。氧化爆发应答的作用是清除病原体，但同时也可能带来免疫病理风险——因为它们可诱导自身细胞发生氧化损伤。为了最大限度降低感染风险，同时减少对自身组织的损伤，氧化爆发的活性必须受到严格的动态平衡调控。当前个体体内促氧化剂与抗氧化剂的水平（即个体氧化状态）可能是影响这一平衡的关键因素，但这一点尚未得到实验验证。本研究以野生捕获的饰纹龙蜥（Ctenophorus pictus）为实验对象，探究在对照条件与大肠杆菌脂多糖（Escherichia coli lipopolysaccharide, LPS）体内免疫刺激过程中，全血中吞噬细胞的免疫刺激型氧化爆发应答强度与个体氧化状态之间的关联。在对照条件下，饰纹龙蜥的氧化状态无法预测其氧化爆发应答强度。与对照组个体相比，经脂多糖注射的个体表现出促氧化剂水平显著升高、抗氧化剂水平显著降低的特征，体现出促/抗氧化平衡的偏移。经脂多糖免疫刺激的蜥蜴，其氧化爆发应答与免疫刺激后细胞外促氧化剂水平呈正相关（反映细胞激活程度），而与免疫刺激前线粒体超氧阴离子水平呈负相关（提示该促氧化剂具有免疫调节作用）。经脂多糖免疫刺激的雄性蜥蜴，其氧化爆发应答水平高于雌性蜥蜴；且与雄性相比，雌性的氧化爆发应答似乎更依赖于抗氧化剂状态。本研究结果证实了"氧化状态可能限制先天免疫系统活性"这一假说。这种限制可能会对自然选择作用于促氧化剂生成过程的方式产生重要影响。