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How Many Parameters Does It Take to Describe Disease Tolerance?
Alexander Louie1,2, Kyung Han Song1, Alejandra Hotson1
1Department of Microbiology and Immunology, Stanford University, Stanford, California, United States of America.
Plos Biology
|April 19, 2016
Summary
This study introduces a new framework to understand disease tolerance in infectious diseases. It reveals that the pathogen, not the immune response, drives damage, paving the way for improved treatments.
Area of Science:
- Infectious disease dynamics
- Host-pathogen interactions
- Mathematical modeling in biology
Background:
- Model organisms are crucial for infectious disease research but lack a unifying framework for translating findings.
- Host variability and lack of conceptual models hinder progress in understanding and treating infectious diseases.
Purpose of the Study:
- To develop a graphical and mathematical framework for studying disease tolerance.
- To uncover previously overlooked parameters in host-pathogen interactions.
- To provide a basis for improved treatment strategies.
Main Methods:
- Developed a simple graphical and mathematical framework to analyze the dose-response curve of health versus microbe load.
- Utilized Drosophila melanogaster challenged with Listeria monocytogenes as a model experimental system.
- Applied sigmoid and logistic models to represent microbe growth, immune response, and disease tolerance.
Main Results:
- Microbe growth, immune response, and disease tolerance were accurately modeled using sigmoid functions.
- Disease tolerance varied with host or pathogen genetics, governed by system sensitivity and maximal effect size.
- Pathogen load, rather than the immune response, was identified as the primary driver of pathology in this model.
Conclusions:
- The developed framework effectively models disease tolerance and its underlying parameters.
- Understanding the circuitry of disease tolerance, driven by the pathogen, enables better treatment selection and development.
- This research offers a new perspective on managing infectious diseases through targeted interventions.
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