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Data from: Health trajectories reveal the dynamic contributions of host genetic resistance and tolerance to infection outcome

Citation

Lough, Graham et al. (2015), Data from: Health trajectories reveal the dynamic contributions of host genetic resistance and tolerance to infection outcome, Dryad, Dataset, https://doi.org/10.5061/dryad.th60q

Abstract

Resistance and tolerance are two alternative strategies hosts can adopt to survive infections. Both strategies may be genetically controlled. To date, the relative contribution of resistance and tolerance to infection outcome is poorly understood. A bioluminescent Listeria monocytogenes (Lm) infection challenge model on four genetically diverse mouse strains was used to study the genetic determination and dynamic contributions of host resistance and tolerance to listeriosis, a serious food-borne infectious disease in humans. Conventional statistical analyses revealed significant genetic variation in both resistance and tolerance, but could not capture the time-dependent relative importance of either strategy. These limitations were overcome by the development of novel statistical tools to analyse individual infection trajectories portraying simultaneous changes in infection severity and health. Based on these tools, early expression of resistance followed later by expression of tolerance, emerged as important hallmarks for surviving Lm infections. Trajectory analysis further revealed that survivors and non-survivors follow distinct infection paths, which are also genetically determined, and provided new survival thresholds as objective endpoints in infection experiments. Future studies may use trajectories as novel traits for mapping and identifying genes that control infection dynamics and outcome. A Matlab script for user-friendly trajectory analysis is provided.

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