title: Differential virulence and disease progression following Mycobacterium tuberculosis complex infection of the common marmoset (Callithrix jacchus).
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.
authors.affiliation: Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute for Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Laura E
authors.initials: LE
authors.lastname: Via
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Weiner
authors.forename: Daniel
authors.initials: D
authors.lastname: Schimel
authors.forename: Philana Ling
authors.initials: PL
authors.lastname: Lin
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Dayao
authors.forename: Sarah L
authors.initials: SL
authors.lastname: Tankersley
authors.forename: Ying
authors.initials: Y
authors.lastname: Cai
authors.forename: M Teresa
authors.initials: MT
authors.lastname: Coleman
authors.forename: Jaime
authors.initials: J
authors.lastname: Tomko
authors.forename: Praveen
authors.initials: P
authors.lastname: Paripati
authors.forename: Marlene
authors.initials: M
authors.lastname: Orandle
authors.forename: Robin J
authors.initials: RJ
authors.lastname: Kastenmayer
authors.forename: Michael
authors.initials: M
authors.lastname: Tartakovsky
authors.forename: Alexander
authors.initials: A
authors.lastname: Rosenthal
authors.forename: Damien
authors.initials: D
authors.lastname: Portevin
authors.forename: Seok Yong
authors.initials: SY
authors.lastname: Eum
authors.forename: Saher
authors.initials: S
authors.lastname: Lahouar
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gagneux
authors.forename: Douglas B
authors.initials: DB
authors.lastname: Young
authors.forename: Joanne L
authors.initials: JL
authors.lastname: Flynn
authors.forename: Clifton E
authors.initials: CE
authors.lastname: Barry
mesh_terms: D000818:Animals; D002144:Callithrix; D004195:Disease Models, Animal; D018450:Disease Progression; D064847:Multimodal Imaging; D009169:Mycobacterium tuberculosis / Q000472:pathogenicity*; D049268:Positron-Emission Tomography; D014057:Tomography, X-Ray Computed; D014376:Tuberculosis / Q000382:microbiology* / Q000473:pathology*; D014774:Virulence