A within-host infection model to explore tolerance and resistance

Area of Science:

• Infectious disease dynamics
• Host-pathogen interactions
• Theoretical biology

Background:

• Host survival during infection hinges on balancing pathogen control (resistance) and damage mitigation (disease tolerance).
• Understanding the interplay between these strategies is crucial for predicting infection outcomes.

Purpose of the Study:

• To develop a theoretical model predicting within-host pathogen dynamics and host survival based on resistance and tolerance.
• To establish a method for empirically distinguishing the effects of resistance and disease tolerance.

Main Methods:

• A deterministic theoretical model simulating host-pathogen immune interactions was developed.
• The model predicts pathogen load dynamics, including Set-Point Pathogen Load (SPPL) and Pathogen Load Upon Death (PLUD).
• Empirical validation was performed using Drosophila melanogaster infected with Providencia rettgeri.

Main Results:

• The model predicts SPPL can transiently indicate lifespan or stably diagnose non-lethal infections.
• PLUD in lethal infections is largely independent of initial conditions and can differentiate resistance from tolerance.
• Empirical data supported model predictions, with wounded/deficient hosts showing higher PLUD and catalase mutants showing lower PLUD.

Conclusions:

• The developed model provides a framework for understanding infection outcomes based on resistance and tolerance.
• PLUD, in conjunction with mortality data, serves as a valuable metric to disentangle the distinct contributions of resistance and disease tolerance.
• This approach offers a novel way to study host defense strategies in empirical systems.