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Published on: September 5, 2017
Rhesus Macaques Are More Susceptible to Progressive Tuberculosis than Cynomolgus Macaques: a Quantitative Comparison
Pauline Maiello1, Robert M DiFazio1, Anthony M Cadena1
1Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Abstract:
In the past 2 decades, it has become increasingly clear that nonhuman primates, specifically macaques, are useful models for human tuberculosis (TB). Several macaque species have been used for TB studies, and questions remain about the similarities and differences in TB pathogenesis among macaque species, which can complicate decisions about the best species for a specific experiment. Here we provide a quantitative assessment, using serial positron emission tomography and computed tomography (PET-CT) imaging and precise quantitative determination of bacterial burdens of low-dose Mycobacterium tuberculosis infection in cynomolgus macaques of Chinese origin, rhesus macaques of Chinese origin, and Mauritian cynomolgus macaques. This comprehensive study demonstrates that there is substantial variability in the outcome of infection within and among species. Overall, rhesus macaques have higher rates of disease progression, more lung, lymph node, and extrapulmonary involvement, and higher bacterial burdens than Chinese cynomolgus macaques. The small cohort of Mauritian cynomolgus macaques assessed here indicates that this species is more similar to rhesus macaques than to Chinese cynomolgus macaques in terms of M. tuberculosis infection outcome. These data provide insights into the differences among species, providing valuable data to the field for assessing macaque studies of TB.
Insights
Nonhuman primates like macaques are valuable models for tuberculosis (TB) research. This study quantifies TB outcomes in different macaque species, revealing significant variability and aiding model selection.
Area of Science:
- Veterinary Medicine
- Infectious Diseases
- Primate Models
Background:
- Nonhuman primates, particularly macaques, are crucial models for studying human tuberculosis (TB).
- Variability in TB pathogenesis among macaque species complicates experimental design.
- Standardized quantitative assessments are needed to compare TB outcomes across macaque models.
Purpose of the Study:
- To quantitatively assess and compare the outcomes of low-dose Mycobacterium tuberculosis infection in Chinese cynomolgus macaques, Chinese rhesus macaques, and Mauritian cynomolgus macaques.
- To identify differences and similarities in TB disease progression and bacterial burden among these macaque species.
- To provide data to guide the selection of appropriate macaque models for TB research.
Main Methods:
- Low-dose Mycobacterium tuberculosis infection was administered to three macaque species.
- Serial positron emission tomography and computed tomography (PET-CT) imaging was used for in-vivo assessment.
- Precise quantitative determination of bacterial burdens was performed.
Main Results:
- Substantial variability in TB infection outcomes was observed within and among the studied macaque species.
- Chinese rhesus macaques exhibited higher disease progression rates, greater lung and lymph node involvement, and higher bacterial burdens compared to Chinese cynomolgus macaques.
- Mauritian cynomolgus macaques showed TB infection outcomes more similar to rhesus macaques than to Chinese cynomolgus macaques.
Conclusions:
- Significant inter-species differences exist in Mycobacterium tuberculosis infection outcomes among macaques.
- Chinese rhesus macaques and Mauritian cynomolgus macaques appear to be more susceptible to TB progression than Chinese cynomolgus macaques.
- These findings offer valuable insights for selecting optimal macaque models in tuberculosis research.
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