Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Department of Pediatrics, Division of Infectious Diseases, UPMC Children's Hospital of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Infect Immun. 2018 Jan 22;86(2). doi: 10.1128/IAI.00505-17. Print 2018 Feb.
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 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 infection outcome. These data provide insights into the differences among species, providing valuable data to the field for assessing macaque studies of TB.
在过去的 20 年中,越来越明显的是,非人类灵长类动物,特别是猕猴,是研究人类结核病(TB)的有用模型。已经有几种猕猴被用于 TB 研究,但对于不同猕猴物种之间的 TB 发病机制的相似性和差异性仍存在疑问,这可能会使选择最适合特定实验的物种变得复杂。在这里,我们使用连续正电子发射断层扫描和计算机断层扫描(PET-CT)成像以及对来自中国的食蟹猕猴、来自中国的恒河猴和毛里求斯食蟹猕猴的低剂量感染的细菌载量进行精确定量测定,对这一问题进行了定量评估。这项综合性研究表明,在种内和种间,感染的结果存在很大的可变性。总的来说,恒河猴的疾病进展率更高,肺部、淋巴结和肺外受累更多,细菌载量也比中国食蟹猕猴更高。我们评估的这一小批毛里求斯食蟹猕猴表明,就感染结果而言,该物种与恒河猴更为相似,而与中国食蟹猕猴则不同。这些数据提供了对物种间差异的深入了解,为评估 TB 猕猴研究提供了有价值的数据。