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Differential virulence and disease progression following Mycobacterium tuberculosis complex infection of the common marmoset (Callithrix jacchus)

Via, Laura E. and Weiner, Danielle M. and Schimel, Daniel and Lin, Philana Ling and Dayao, Emmanuel and Tankersley, Sarah L. and Cai, Ying and Coleman, M. Teresa and Tomko, Jaime and Paripati, Praveen and Orandle, Marlene and Kastenmayer, Robin J. and Tartakovsky, Michael and Rosenthal, Alexander and Portevin, Damien and Eum, Seok Yong and Lahouar, Saher and Gagneux, Sebastien and Young, Douglas B. and Flynn, Joanne L. and Barry, Clifton E.. (2013) Differential virulence and disease progression following Mycobacterium tuberculosis complex infection of the common marmoset (Callithrix jacchus). Infection and immunity, Vol. 81, H. 8. pp. 2909-2919.

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Official URL: http://edoc.unibas.ch/dok/A6165163

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Abstract

Existing small-animal models of tuberculosis (TB) rarely develop cavitary disease, limiting their value for assessing the biology and dynamics of this highly important feature of human disease. To develop a smaller primate model with pathology similar to that seen in humans, we experimentally infected the common marmoset (Callithrix jacchus) with diverse strains of Mycobacterium tuberculosis of various pathogenic potentials. These included recent isolates of the modern Beijing lineage, the Euro-American X lineage, and M. africanum. All three strains produced fulminant disease in this animal with a spectrum of progression rates and clinical sequelae that could be monitored in real time using 2-deoxy-2-[(18)F]fluoro-d-glucose (FDG) positron emission tomography (PET)/computed tomography (CT). Lesion pathology at sacrifice revealed the entire spectrum of lesions observed in human TB patients. The three strains produced different rates of progression to disease, various extents of extrapulmonary dissemination, and various degrees of cavitation. The majority of live births in this species are twins, and comparison of results from siblings with different infecting strains allowed us to establish that the infection was highly reproducible and that the differential virulence of strains was not simply host variation. Quantitative assessment of disease burden by FDG-PET/CT provided an accurate reflection of the pathology findings at necropsy. These results suggest that the marmoset offers an attractive small-animal model of human disease that recapitulates both the complex pathology and spectrum of disease observed in humans infected with various M. tuberculosis strain clades.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Tuberculosis Research (Gagneux)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
UniBasel Contributors:Gagneux, Sebastien
Item Type:Article, refereed
Article Subtype:Research Article
Bibsysno:Link to catalogue
Publisher:American Society for Microbiology
ISSN:1098-5522
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:27 Feb 2014 15:46
Deposited On:27 Feb 2014 15:46

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