Animal model of Mycobacterium abscessus lung infection
Animal model of Mycobacterium abscessus lung infection
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DOI：
10.1189/jlb.1007696
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发表时间：
2008-06-01
影响因子：
5.5
通讯作者：
Chan, Edward D.
中科院分区：
文献类型：
--
作者：
Ordway, Diane;Henao-Tamayo, Marcela;Chan, Edward D.
在美国，由脓肿分枝杆菌引起的慢性肺部疾病是一种新兴的感染。我们描述了小鼠和豚鼠感染脓肿分枝杆菌后的肺部免疫反应。C57BL/6和瘦素缺乏的ob/ob小鼠受到低剂量气雾剂（LDA）的攻击，没有发生感染。然而，当受到高剂量气溶胶（HDA）攻击时，C57BL/6和ob/ob小鼠发生了确定的感染和肺部免疫反应，包括ifn - γ + CD4+ T细胞的早期涌入；这种免疫反应在两株小鼠成功清除脓肿分枝杆菌之前，尽管在ob/ob小鼠中分枝杆菌的清除延迟。受感染的豚鼠在第60天肺部淋巴细胞流入增加，细菌清除。与C57BL/6和ob/ob小鼠和豚鼠相比，ifn - γ敲除（GKO）小鼠受到LDA或HDA脓肿分枝杆菌的攻击，尽管T细胞、巨噬细胞和树突状细胞大量涌入，但仍表现出进行性肺部感染，最终导致肺广泛实变。此外，在HDA刺激下，GKO小鼠的肺部出现了产生IL-4和il -10的CD4+和CD8+ T细胞。综上所述，ifn - γ在宿主对脓疡分枝杆菌的防御中起着至关重要的作用。由于对脓肿支原体有效的药物数量有限，GKO小鼠为新型药物的体内试验提供了模型。
Chronic lung disease as a result of Mycobacterium abscessus is an emerging infection in the United States. We characterized the lung immune responses in mice and guinea pigs infected with M. abscessus. C57BL/6 and leptin-deficient ob/ob mice challenged with a low-dose aerosol (LDA) of M. abscessus did not develop an infection. However, when challenged with a high-dose aerosol (HDA), C57BL/6 and ob/ob mice developed an established infection and a pulmonary immune response consisting of an early influx of IFN-gamma+ CD4+ T cells; this immune response preceded the successful clearance of M. abscessus in both strains of mice, although mycobacterial elimination was delayed in the ob/ob mice. Infected guinea pigs showed an increased influx of lymphocytes into the lungs with bacterial clearance by Day 60. In contrast to the C57BL/6 and ob/ob mice and guinea pigs, IFN-gamma knockout (GKO) mice challenged with a LDA or HDA of M. abscessus showed a progressive lung infection despite a robust influx of T cells, macrophages, and dendritic cells, culminating in extensive lung consolidation. Furthermore, with HDA challenge of the GKO mice, emergence of IL-4- and IL-10-producing CD4+ and CD8+ T cells was seen in the lungs. In conclusion, IFN-gamma is critically important in the host defense against M. abscessus. As the number of effective drugs against M. abscessus is limited, the GKO mice provide a model for in vivo testing of novel drugs.