Low-dose immune challenges result in detectable levels of oxidative damage

Abstract

Infection can result in substantial costs to animals, so they frequently respond by removing infectious agents with an immune response. However, immune responses entail their own costs, including up-regulation of processes that destroy pathogens (e.g., the production of reactive oxygen species), and processes that limit the extent of self-damage during the immune response (e.g., production of anti-inflammatory proteins such as haptoglobin). Here, we simulated bacterial infection across a 1,000-fold range using lipopolysaccharide (LPS) administered to northern bobwhite quail (Colinus virginianus), and quantified metrics related to pro-inflammatory conditions (i.e., generation of oxidative damage [d-ROMs], depletion of antioxidant capacity), anti-inflammatory mechanisms (i.e., production of haptoglobin, expression of the enzyme heme oxygenase, production of the organic molecule biliverdin), and nutritional physiology (e.g., circulating triglyceride levels, maintenance of body mass). We detected increases in levels of haptoglobin and d-ROMs even at LPS doses that are 1/1,000th the concentration of doses frequently used in ecoimmunological studies, while loss of body mass and decreases in circulating triglycerides manifested only in individuals receiving the highest dose of LPS (1 mg LPS/ kg body mass), highlighting variation among dose-dependent responses. Additionally, individuals that lost body mass during the course of the experiment had lower levels of circulating triglycerides, and those with more oxidative damage had greater levels of heme oxygenase expression, which highlights the complex interplay between pro- and anti-inflammatory processes. Because low doses of LPS may simulate natural infection levels, variation in dose-dependent physiological responses may be particularly important in modeling how free-living animals navigate immune challenges.