Differential Virulence and Disease Progression following Mycobacterium tuberculosis Complex Infection of the Common Marmoset (Callithrix jacchus)
Differential Virulence and Disease Progression following Mycobacterium tuberculosis Complex Infection of the Common Marmoset (Callithrix jacchus)
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DOI：
10.1128/iai.00632-13
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发表时间：
2013-08-01
影响因子：
3.1
通讯作者：
Barry, Clifton E., III
中科院分区：
文献类型：
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作者：
Via, Laura E.;Weiner, Danielle M.;Barry, Clifton E., III
现有的结核病（TB）小动物模型很少出现空洞病，这限制了它们在评估人类疾病这一非常重要特征的生物学和动力学方面的价值。为了开发病理学与人类相似的较小灵长类动物模型，我们通过实验用具有各种致病潜力的结核分枝杆菌菌株感染普通狨猴（Callithrix jacchus）。其中包括现代北京谱系、欧美 X 谱系和 M. africanum 的最新分离株。所有三种菌株均在该动物中产生了暴发性疾病，并具有一系列进展率和临床后遗症，可以使用 2-脱氧-2-[F-18]氟-D-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。处死时的病变病理学揭示了在人类结核病患者中观察到的整个病变范围。这三种菌株产生不同的疾病进展速度、不同程度的肺外传播以及不同程度的空化。该物种的大多数活产都是双胞胎，通过比较具有不同感染菌株的兄弟姐妹的结果，我们可以确定感染具有高度可重复性，并且菌株的毒力差异不仅仅是宿主变异。 FDG-PET/CT 对疾病负担的定量评估准确反映了尸检时的病理结果。这些结果表明，狨猴提供了一种有吸引力的人类疾病小动物模型，它概括了在感染各种结核分枝杆菌菌株进化枝的人类中观察到的复杂病理学和疾病谱。
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-[F-18]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.