Mycobacterium abscessus morphotype comparison in a murine model.

Mycobacterium abscessus morphotype comparison in a murine model.
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DOI:
10.1371/journal.pone.0117657
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发表时间:
2015
期刊:
影响因子:
3.7
通讯作者:
Nichols DP
Nichols DP
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Caverly LJ;Caceres SM;Fratelli C;Happoldt C;Kidwell KM;Malcolm KC;Nick JA;Nichols DP

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脓肿分枝杆菌(M.脓肿)的肺部感染在患有囊性纤维化等肺部疾病的患者中越来越普遍。脓肿分枝杆菌有光滑型和粗糙型两种形态,但形态型对毒力的影响尚不清楚。我们开发了肺部脓肿分枝杆菌感染的免疫活性小鼠模型,并测试了脓肿分枝杆菌形态类型之间宿主炎症反应的差异。脓肿分枝杆菌的光滑和粗糙形态型是从相同的美国典型培养物保藏中心菌株中分离出来的。野生型和囊性纤维化小鼠气管内接种已知量的悬浮在纤维蛋白塞中的脓肿分枝杆菌。处死时,收集并培养肺和脾组织以及支气管肺泡灌洗液。分析支气管肺泡灌洗液的白细胞计数、差异和细胞因子表达。所有组中接种后 3 天和 14 天均出现脓肿分枝杆菌肺部感染,其水平高于全身感染。接种后 14 天,野生型 (p = 0.01) 和囊性纤维化 (p<0.01) 小鼠中,与平滑形态型小鼠相比,接种粗糙形态型脓肿分枝杆菌可产生更多的支气管肺泡灌洗液中性粒细胞。 12/57 (21%) 的小鼠体内自发地从光滑形态转变为粗糙形态。与未发生形态型转换的小鼠相比,这些小鼠的体重减轻趋势更大。在所描述的脓肿分枝杆菌感染的纤维蛋白栓模型中,通过光滑和粗糙的形态类型实现了肺部感染,且全身传播最小。在该模型中,基于支气管肺泡灌洗液中性粒细胞水平,粗糙形态型脓肿分枝杆菌比平滑形态型引起更大的宿主炎症反应。
Pulmonary infections with Mycobacterium abscessus (M. abscessus) are increasingly prevalent in patients with lung diseases such as cystic fibrosis. M. abscessus exists in two morphotypes, smooth and rough, but the impact of morphotype on virulence is unclear. We developed an immune competent mouse model of pulmonary M. abscessus infection and tested the differences in host inflammatory response between the morphotypes of M. abscessus. Smooth and rough morphotypes of M. abscessus were isolated from the same American Type Culture Collection strain. Wild type and cystic fibrosis mice were intratracheally inoculated with known quantities of M. abscessus suspended in fibrin plugs. At the time of sacrifice lung and splenic tissues and bronchoalveolar lavage fluid were collected and cultured. Bronchoalveolar lavage fluid was analyzed for leukocyte count, differential and cytokine expression. Pulmonary infection with M. abscessus was present at both 3 days and 14 days post-inoculation in all groups at greater levels than systemic infection. Inoculation with M. abscessus rough morphotype resulted in more bronchoalveolar lavage fluid neutrophils compared to smooth morphotype at 14 days post-inoculation in both wild type (p = 0.01) and cystic fibrosis (p<0.01) mice. Spontaneous in vivo conversion from smooth to rough morphotype occurred in 12/57 (21%) of mice. These mice trended towards greater weight loss than mice in which morphotype conversion did not occur. In the described fibrin plug model of M. abscessus infection, pulmonary infection with minimal systemic dissemination is achieved with both smooth and rough morphotypes. In this model M. abscessus rough morphotype causes a greater host inflammatory response than the smooth based on bronchoalveolar lavage fluid neutrophil levels.
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发表时间: 2008-10-01
影响因子: 9.4
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发表时间: 2009-05-01
期刊: Proceedings of the American Thoracic Society
影响因子: --
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影响因子: 5.5
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