Comparative analysis of mycobacterial infections in susceptible I/St and resistant A/Sn inbred mice
Comparative analysis of mycobacterial infections in susceptible I/St and resistant A/Sn inbred mice
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DOI：
10.1054/tuld.1999.0225
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发表时间：
2000-01-01
期刊：
影响因子：
--
通讯作者：
Apt, AS
中科院分区：
文献类型：
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作者：
Nikonenko, BV;Averbakh, MM;Apt, AS
设定：动物模型的可用性和适当使用对于更好和更详细地了解人类分枝杆菌疾病发展的遗传、免疫和病理机制具有重要意义。目的：定义一种用于结核病严重程度的小鼠模型，该模型可以容易地适应于宿主对结核分枝杆菌感染的反应的遗传和免疫学分析。设计：我们在这里描述了两种近交系小鼠，I/St和A/Sn（均为Nramp 1 '），它们在常用的M强毒株和减毒株感染敏感性参数上有很大差异。结果：用高剂量H37 Rv强毒感染后，NN. I/St小鼠的平均存活时间比它们的耐药A/Sn小鼠短2倍以上，并且严重体重减轻（恶病质）的发作和进展更快。此外，I/St小鼠支持20-100倍的M的增殖。I/St小鼠的高易感性还通过更严重的肺组织病理学反映，如通过更大和更多的肺肉芽肿和巨噬细胞主导的细胞浸润所证明的。最后，我们确定I/St也不能控制减毒H37 Ra M的感染。结核和两株M. bovis（BCG和Ravenel）表明I/St小鼠品系对分枝杆菌infections.Conclusions的超敏感性：我们的实验结果表明，耐药A/Sn和敏感的I/St小鼠的比较分析提供了一种理想的方法来研究宿主依赖方面的结核病易感性的控制条件下提供的动物模型。(C)2000年哈考特出版社有限公司
Setting: The availability and appropriate use of animal models is of significant importance for a better and more detailed understanding of the genetic, immunological and pathological mechanisms underlying the development of mycobacterial disease in humans.Objective: To define a mouse model for tuberculosis severity that can be easily adapted to genetic and immunological analysis of host repsonse to Mycobacterium tuberculosis infection.Design: We describe here two inbred strains of mice, I/St and A/Sn (both Nramp1'), that differ vastly in commonly used parameters of susceptibility to infection with virulent and attenuated strains of M. tuberculosis.Results: Following infection with a high dose of virulent H37Rv. nn. tuberculosis and compared to their resistant A/Sn counterparts, I/St mice displayed more than a 2-fold shorter mean survival time and a more rapid onset and progression of severe body weight loss (cachexia). Moreover, I/St mice supported 20-100-fold higher multiplication of M. tuberculosis following challenge with H37Rv over a large range of infectious inocula.The high susceptibility of I/St mice was also reflected by more severe lung histopathology as evidenced by larger and more numerous lung granuloma and macrophage dominated cellular infiltrates. Finally, we determined that I/St are also unable to control infection with attenuated H37Ra M. tuberculosis and two strains of M. bovis (BCG and Ravenel) indicating hyper-susceptibility of the I/St mouse strain to mycobacterial infections.Conclusions: The results of our experiments suggest that comparative analysis of resistant A/Sn and susceptible I/St mice provides an ideal way to study host dependent aspects of tuberculosis susceptibility under the controlled conditions provided by an animal model. (C) 2000 Harcourt Publishers Ltd.