Turner Oliver C, Keefe Robert G, Sugawara Isamu, Yamada Hiroyuki, Orme Ian M
Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado 80523, USA.
Infect Immun. 2003 Sep;71(9):5266-72. doi: 10.1128/IAI.71.9.5266-5272.2003.
Inbred mice differ in their abilities to control the growth of Mycobacterium tuberculosis in the lung and can as a result be regarded as either resistant or susceptible strains. In this study we report that the SWR mouse is both highly susceptible and in addition appears incapable of establishing a characteristic state of chronic disease after low-dose aerosol infection. In comparison to C57BL/6 mice, SWR mice were unable to contain the bacterial load in the lungs, resulting in progressive fatal disease. Histologic analysis of the lung tissue revealed evidence of a florid inflammatory cell response in the SWR mice leading to degeneration and necrosis and consolidation of a large percentage of the lung surface area. Digestion of infected lungs and analysis by flow cytometry demonstrated an initially similar but eventually higher number of lymphocytes accumulating in the SWR mice. Additionally, in contrast to the C57BL/6 mice, SWR mice had a significantly lower percentage of CD4 T cells in the lungs showing evidence of proliferation and positive intracellular staining for gamma interferon during the first two months of infection, and a lower percentage of both CD4 and CD8T cells exhibiting differentiation to an effector/memory phenotype during the first month of infection. We propose that further investigation of the SWR mouse may provide a new animal model for immunocompetent individuals apparently unable to effectively control the growth of M. tuberculosis in the lung.
近交系小鼠在控制肺部结核分枝杆菌生长的能力上存在差异,因此可被视为抗性或易感品系。在本研究中,我们报告SWR小鼠不仅高度易感,而且在低剂量气溶胶感染后似乎无法建立慢性疾病的特征状态。与C57BL/6小鼠相比,SWR小鼠无法控制肺部的细菌载量,导致进行性致命疾病。肺组织的组织学分析显示,SWR小鼠有明显的炎症细胞反应,导致肺表面积的很大一部分发生变性、坏死和实变。对感染的肺进行消化并通过流式细胞术分析表明,SWR小鼠中最初积累的淋巴细胞数量相似,但最终更多。此外,与C57BL/6小鼠相比,在感染的前两个月,SWR小鼠肺部显示增殖证据且γ干扰素细胞内染色呈阳性的CD4 T细胞百分比显著降低,在感染的第一个月,表现出向效应/记忆表型分化的CD4和CD8 T细胞百分比均较低。我们建议,对SWR小鼠的进一步研究可能为明显无法有效控制肺部结核分枝杆菌生长的免疫活性个体提供一种新的动物模型。