Tuberculosis Research Section, Laboratory of Clinical Infectious Diseases, National Institute for Allergy and Infectious Disease, National Institutes of Health, Bethesda, Maryland, USA.
Infect Immun. 2013 Aug;81(8):2909-19. doi: 10.1128/IAI.00632-13. Epub 2013 May 28.
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.
现有的结核病（TB）小动物模型很少发展为空洞性疾病，限制了它们用于评估人类疾病这一高度重要特征的生物学和动态变化的价值。为了开发一种具有与人类相似病理学的小型灵长类动物模型，我们用不同致病性的结核分枝杆菌菌株对普通狨猴（Callithrix jacchus）进行了实验性感染，这些菌株包括现代北京谱系、欧洲-美洲 X 谱系和 M. africanum 的近期分离株。所有三种菌株都导致了这种动物的暴发性疾病，其进展速度和临床后果范围可通过使用 2-脱氧-2-[(18)F]氟代葡萄糖（FDG）正电子发射断层扫描（PET）/计算机断层扫描（CT）进行实时监测。在进行尸检时，病变病理学显示了在人类结核病患者中观察到的所有病变谱。三种菌株导致疾病的进展速度不同，肺外传播的程度不同，以及空洞的程度不同。该物种的大多数活产是双胞胎，对具有不同感染菌株的兄弟姐妹的结果进行比较，使我们能够确定该感染具有高度可重复性，并且菌株的差异毒力不是简单的宿主变化。FDG-PET/CT 对疾病负担的定量评估准确反映了尸检时的病理学发现。这些结果表明，狨猴提供了一种有吸引力的人类疾病的小型动物模型，既再现了人类感染各种结核分枝杆菌菌株谱系时观察到的复杂病理学，也再现了疾病谱。
