Ramos Laylaa, Obregon-Henao Andres, Henao-Tamayo Marcela, Bowen Richard, Lunney Joan K, Gonzalez-Juarrero Mercedes
Cell and Molecular Biology Colorado State University, Fort Collins, CO 80523, USA.
Department of Microbiology, Immunology and Pathology, Colorado State University, Campus Delivery 1682, Fort Collins, CO 80523, USA.
Tuberculosis (Edinb). 2017 Sep;106:91-98. doi: 10.1016/j.tube.2017.07.003. Epub 2017 Jul 14.
In endemic countries more than 20% of tuberculosis (TB) cases are in infants and children. Current animal models study TB during adulthood but animal models for infant TB are scarce. Here we propose that minipigs can be used as an animal model to study adult, adolescent and infant TB including natural transmission. In these studies, two-month old minipigs (representing infant age in humans) and six-month old minipigs (representing adolescence in humans) were infected via the aerosol route with hyper-virulent clinical strain W-Beijing Mycobacterium tuberculosis (Mtb) HN878 and were monitored for 11 or 36 weeks post-challenge, respectively. In the same studies, infected and unchallenged animals were housed together. Viable bacteria were recovered from pulmonary and thoracic lymph nodes from both -infected and their initially unchallenged natural contacts. Bacillary load, gross lesions and histopathology revealed similarities to the spectrum of disease observed in human TB. The study did not reach terminal end point, thus it was not possible to annotate definitive clinical symptoms of active TB. The results demonstrated that minipigs are experimental hosts of Mtb HN878, and the pathology developed in their lungs resembles pathological findings described in human TB. Importantly, within communities of Mtb infected minipigs natural transmission occurs.
在结核病流行国家，超过20%的结核病病例发生在婴幼儿身上。目前的动物模型研究的是成年期的结核病，但针对婴幼儿结核病的动物模型却很稀缺。在此，我们提出小型猪可作为一种动物模型，用于研究成人、青少年和婴幼儿结核病，包括自然传播。在这些研究中，分别将两个月大的小型猪（代表人类的婴儿期）和六个月大的小型猪（代表人类的青春期）通过气溶胶途径感染高毒力临床菌株W-北京结核分枝杆菌（Mtb）HN878，并在攻毒后分别监测11周或36周。在同一研究中，将感染和未感染的动物饲养在一起。从感染动物及其最初未感染的自然接触动物的肺和胸段淋巴结中均分离出了活细菌。细菌载量、大体病变和组织病理学显示与人类结核病所观察到的疾病谱相似。该研究未达到终点，因此无法明确标注活动性结核病的明确临床症状。结果表明，小型猪是Mtb HN878的实验宿主，其肺部出现的病理变化与人类结核病中描述的病理发现相似。重要的是，在感染Mtb的小型猪群体中发生了自然传播。
