Genetically diverse mice are novel and valuable models of age-associated susceptibility to Mycobacterium tuberculosis
David E Harrison1, Clinton M Astle1, M Khalid Khan Niazi2
1The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609 USA.
Background:
Tuberculosis, the disease due to Mycobacterium tuberculosis, is an important cause of morbidity and mortality in the elderly. Use of mouse models may accelerate insight into the disease and tests of therapies since mice age thirty times faster than humans. However, the majority of TB research relies on inbred mouse strains, and these results might not extrapolate well to the genetically diverse human population. We report here the first tests of M. tuberculosis infection in genetically heterogeneous aging mice, testing if old mice benefit from rapamycin.
Findings:
We find that genetically diverse aging mice are much more susceptible than young mice to M. tuberculosis, as are aging human beings. We also find that rapamycin boosts immune responses during primary infection but fails to increase survival.
Conclusions:
Genetically diverse mouse models provide a valuable resource to study how age influences responses and susceptibility to pathogens and to test interventions. Additionally, surrogate markers such as immune measures may not predict whether interventions improve survival.
Insights
Aging, genetically diverse mice show increased susceptibility to tuberculosis (TB). While rapamycin improved immune responses in old mice, it did not enhance survival, highlighting the need for better TB interventions.
Area of Science:
- Immunology
- Gerontology
- Infectious Diseases
Background:
- Tuberculosis (TB) disproportionately affects the elderly.
- Current mouse models often use inbred strains, limiting relevance to diverse human populations.
- Aging mice offer a faster model to study age-related disease and therapeutic responses.
Purpose of the Study:
- To investigate Mycobacterium tuberculosis infection in genetically heterogeneous aging mice.
- To evaluate the efficacy of rapamycin as an intervention in aging mice with TB.
Main Methods:
- Infection of genetically diverse young and old mice with Mycobacterium tuberculosis.
- Assessment of susceptibility and survival rates.
- Evaluation of rapamycin's impact on immune responses and survival.
Main Results:
- Genetically diverse aging mice exhibited significantly higher susceptibility to M. tuberculosis compared to young mice.
- Rapamycin enhanced immune responses during primary infection but did not improve survival rates.
- Aging and genetic diversity are critical factors in TB susceptibility.
Conclusions:
- Genetically diverse aging mouse models are valuable for studying age-related disease and testing interventions.
- Immune markers may not accurately predict improved survival outcomes for TB interventions.
- Further research is needed to develop effective TB therapies for the elderly.
