Health trajectories reveal the dynamic contributions of host genetic resistance and tolerance to infection outcome.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractResistance 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. Here, we use a bioluminescent Listeria monocytogenes (Lm) infection challenge model to study the genetic determination and dynamic contributions of host resistance and tolerance to listeriosis in four genetically diverse mouse strains. Using conventional statistical analyses, we detect significant genetic variation in both resistance and tolerance, but cannot capture the time-dependent relative importance of either host strategy. We overcome these limitations through 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 by expression of tolerance emerge as important hallmarks for surviving Lm infections. Our trajectory analysis further reveals that survivors and non-survivors follow distinct infection paths (which are also genetically determined) and provides 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.
CitationHealth trajectories reveal the dynamic contributions of host genetic resistance and tolerance to infection outcome. 2015, 282 (1819): Proc. Biol. Sci.
AffiliationHelmholtz Centre for Infection Research, Inhoffenstr.7, 28124 Braunschweig, Germany.
The following license files are associated with this item:
- Alteration of non-specific resistance to infection with Listeria monocytogenes.
- Authors: Wirsing von König CH, Heymer B, Finger H, Emmerling P, Hof H
- Issue date: 1988
- Measuring bacterial load and immune responses in mice infected with Listeria monocytogenes.
- Authors: Wang N, Strugnell R, Wijburg O, Brodnicki T
- Issue date: 2011 Aug 9
- Phenotypic expression of genetically controlled host resistance to Listeria monocytogenes.
- Authors: Skamene E, Kongshavn PA
- Issue date: 1979 Jul
- With-in host dynamics of L. monocytogenes and thresholds for distinct infection scenarios.
- Authors: Rahman A, Munther D, Fazil A, Smith B, Wu J
- Issue date: 2018 Oct 7
- The timing of IFNβ production affects early innate responses to Listeria monocytogenes and determines the overall outcome of lethal infection.
- Authors: Pontiroli F, Dussurget O, Zanoni I, Urbano M, Beretta O, Granucci F, Ricciardi-Castagnoli P, Cossart P, Foti M
- Issue date: 2012