Progression of chronic pulmonary tuberculosis in mice aerogenically infected with virulent Mycobacterium tuberculosis
Progression of chronic pulmonary tuberculosis in mice aerogenically infected with virulent Mycobacterium tuberculosis
复制标题
DOI：
10.1016/s0962-8479(97)90016-2
复制
发表时间：
1997-01-01
期刊：
影响因子：
--
通讯作者：
Orme, IM
中科院分区：
文献类型：
--
作者：
Rhoades, ER;Frank, AA;Orme, IM
在小鼠和其他动物模型(如豚鼠或兔子)对结核分枝杆菌的肺肉芽肿反应方面，有几个关键的差异。一个关键的区别是在免疫正常的小鼠的肺部病变中明显缺乏中央干酪性坏死。为了确定正常小鼠是否能对高毒力的结核分枝杆菌临床分离株产生这种病理反应，用三种不同毒株的不同剂量的空气感染C57BL/6小鼠，并对肉芽肿性反应的发展进行了长达一年的跟踪。虽然这种情况没有在这些小鼠的肺部引起干酪性坏死，但所有的感染都引起了肉芽肿性反应，进展相似。我们在这里提出了一份描述性报告，描述了肺结核在小鼠肺部的大体病理进展。在每个病例中，疾病进展分为五个不同的阶段，根据几个标准来划分，包括肉芽肿受累的程度，存在的细胞类型，淋巴细胞组织的程度，以及是否存在破坏性后遗症，如呼吸道上皮侵蚀和呼吸道碎片。增加接种物的大小或由毒力更强的分枝杆菌菌株引起沿这五个阶段的更快的疾病进展。强毒株的感染没有得到解决，肉芽肿反应的后期恰好伴随着感染肺中细菌负荷的增加和有组织淋巴细胞的丧失，这最终导致宿主死亡。这些结果表明，虽然C57BL/6小鼠没有表现为干酪型肺结核，但它们表现出同样致病的肉芽肿反应，表现为慢性间质纤维化反应，在肺内有组织的淋巴细胞参与减弱时未能遏制感染。
There are several critical differences in the pulmonary granulomatous response to Mycobacterium tuberculosis between the mouse and other animal models such as the guinea pig or rabbit. One key difference is a conspicuous lack of central caseating necrosis in pulmonary lesions of immunologically intact mice. To determine whether normal mice could develop such pathology in response to highly virulent clinical isolates of M. tuberculosis, C57BL/6 mice were infected aerogenically with varying doses of three different strains, and the development of a granulomatous response was followed for as long as a year. Whereas such conditions failed to induce caseating necrosis in the lungs of these mice, all of the infections induced a granulomatous response which progressed similarly. We present here a descriptive report of the gross pathological progression of tuberculosis in the lungs of the mice. In each case, the disease progressed in five discrete stages, which were delineated on the basis of several criteria including the extent of granulomatous involvement, the cell types present, the degree of lymphocyte organization, and the presence of destructive sequelae such as airway epithelium erosion and airway debris. Quicker progression of disease along these five stages was induced by increasing the size of the inoculum or by the more virulent mycobacterial strains. The infections with the virulent strains were not resolved, and the later stages of the granulomatous response coincided with an increasing bacillary load and a loss of organized lymphocytes in the infected lungs which ultimately resulted in the death of the host. These results indicate that although C57BL/6 mice do not manifest a caseating form of pulmonary tuberculosis, they manifest an equally pathogenic granulomatous response which appears as a chronic interstitial fibrosing response that fails to contain the infection at a time that organized lymphocyte involvement wanes in the lung.