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Predicting the outcome of infectious diseases: variability among inbred mice as a new and powerful tool for biomarker
Miriam E Martin1, Jacquelyn A Dieter, Zheng Luo
1The Center for Comparative Medicine, University of California, Davis, California, USA.
Abstract:
Individuals respond differently to infectious diseases. Even among inbred mice that are presumed to be genetically identical, the response to a microbial pathogen is variable, which is generally thought to reflect experimental inconsistencies, technical errors, and stochastic processes. Here we describe the remarkable observation that the variability of Helicobacter pylori colonization density in the stomachs of experimentally infected C57BL/6J mice is tightly correlated with weight loss and viral load after a challenge with influenza virus, though H. pylori infection per se does not affect influenza and vice versa. Since these two infectious agents are found in different tissue compartments and are detected using unrelated methods, the correlation in microbial burden must represent a biological measure of disease susceptibility among genetically nearly identical individuals and not technical or stochastic factors. We hypothesize that inbred mice represent a powerful new tool for the identification of biomarkers to predict the outcome of infectious diseases.
Insights
Variability in Helicobacter pylori infection in mice unexpectedly correlated with influenza outcomes. This suggests a biological basis for disease susceptibility, not just random chance or errors.
Area of Science:
- Immunology
- Microbiology
- Infectious Diseases
Background:
- Individual responses to infectious diseases vary, even in genetically identical populations.
- This variability is often attributed to experimental error or random chance.
- Understanding disease susceptibility in genetically similar individuals is crucial.
Purpose of the Study:
- To investigate the source of variability in Helicobacter pylori colonization density in C57BL/6J mice.
- To determine if this variability correlates with responses to other infections, such as influenza.
- To explore the potential of inbred mice as models for identifying disease susceptibility biomarkers.
Main Methods:
- Experimentally infected C57BL/6J mice with Helicobacter pylori.
- Challenged infected mice with influenza virus.
- Measured Helicobacter pylori colonization density, mouse weight loss, and influenza viral load.
Main Results:
- Variability in H. pylori colonization density strongly correlated with weight loss and viral load after influenza challenge.
- H. pylori infection did not affect influenza infection, and vice versa.
- The correlation persisted despite the pathogens residing in different tissues and being detected by unrelated methods.
Conclusions:
- The observed correlation suggests a biological basis for disease susceptibility in genetically similar individuals.
- Inbred mice can serve as a valuable model for discovering biomarkers that predict infectious disease outcomes.
- This finding challenges the assumption that variability in controlled experiments is solely due to technical or stochastic factors.
