Natural variation in host defense strategies impacts both host and pathogen fitness

O_LIAnimals ranging from mosquitoes to humans often vary their feeding behavior when infected or merely exposed to pathogens. For example, some individuals drastically reduce their food intake ( illness-mediated anorexia) while others increase food intake ( hyperphagia). While these so-called sickness behaviors are well documented, their functional consequences remain poorly resolved. C_LIO_LIHere, we examine links between natural genetic variation in susceptibility to infection, feeding behaviors, multiple traits of the host, and within-host pathogen production. Using a zooplankton host (Daphnia dentifera) and a fungal pathogen (Metschnikowia bicuspidata) as a case study, we show that genotypic and dose-dependent variation in feeding behaviors are associated with both resistance and tolerance mechanisms. C_LIO_LIIn one genotype, immune-mediated anorexia was associated with increased tolerance to infection; unlike other genotypes, these individuals did not upregulate phenoloxidase activity, but lived longer, had the highest overall fecundity, and produced higher pathogen loads, despite their reduced growth rates and resultant smaller body sizes. In these hosts, peak parasite load remained unchanged, suggesting a tolerance mechanism that offset fecundity costs. C_LIO_LIIn other genotypes, feeding behaviors followed either a flat or hump-shaped pattern with pathogen dose, exhibiting hyperphagia at intermediate doses and anorexia at higher doses. In these cases, anorexia functioned primarily in resistance. C_LIO_LIOur results suggest that infection-mediated changes in host feeding behavior -- which are traditionally interpreted as immunopathology -- may in fact serve as crucial components of host defense strategies. Moreover, these phenomena vary across host genotypes, and were associated with apparent trade-offs with another melanization component of immune defense. Together, these results underscore that while resistance and tolerance are typically viewed as alternative and fixed defense strategies, the immense genetic diversity for immune defense may result in more of a plastic spectrum spanning a gradient from resistance to tolerance. C_LI