The dynamics of tolerance and resistance in heterogeneous environments. Virginia Howick, Brian Lazzaro. Cornell University, Ithaca, NY.

   Defense against pathogenic infection comes as a combination of resistance and tolerance. Resistance is the hosts ability to limit pathogen burden, whereas tolerance is the hosts ability to limit the health or fitness effects of that burden. This distinction recognizes that the fittest host may not have the most aggressive immune system. Studies of animal defense have focused almost completely on resistance to infection, while ignoring potential tolerance mechanisms. Using outbred genotypes derived from the Drosophila Genetic Reference Panel, we have dissected the relative contributions of resistance and tolerance to defense across dietary environments. We measured pathogen load, survival, and change in fecundity over five days after infection with Providencia rettgeri. Using a mathematical framework that allows for quantitative definitions of both resistance and tolerance, we were able to measure variation in both components and the relationship between them. It is possible to infer evolutionary costs associated with each strategy, and we note that the relative balance changes across dietary environment and over time. Our quantitative definitions of resistance and tolerance recognize that infection status is not a dichotomous state, but a continuum that may yield different defense strategies in different contexts. We have also provided a framework for understanding the evolutionary constraints and trajectories of host defense, as well as how the collection of defense strategies a host employs could influence host-pathogen co-evolution and the transmission of infectious disease.