Widespread bronchogenic dissemination makes DBA/2 mice more susceptible than C57BL/6 mice to experimental aerosol infection with Mycobacterium tuberculosis
Widespread bronchogenic dissemination makes DBA/2 mice more susceptible than C57BL/6 mice to experimental aerosol infection with Mycobacterium tuberculosis
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DOI：
10.1128/iai.71.10.5845-5854.2003
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发表时间：
2003-10-01
影响因子：
3.1
通讯作者：
Ausina, V
中科院分区：
文献类型：
--
作者：
Cardona, PJ;Gordillo, S;Ausina, V
我们使用了小鼠模型的气溶胶诱导的实验性结核病，以评估耐药C57 BL/6小鼠和敏感DBA/2小鼠的结核分枝杆菌的四个临床分离株和参考菌株的影响。进行了组织学研究和检测25种可能参与感染的细胞因子。DBA/2小鼠支气管肺泡灌洗液和肺组织中的杆菌浓度较高。此外，由于感染的泡沫巨噬细胞从肉芽肿迁移到相邻肺泡间隙的速率增加，这些小鼠在实质中表现出较大的肉芽肿浸润。从感染后第3周开始，C57 BL/6小鼠中观察到的杆菌浓度和肺浸润的更好控制可能是由于其较高的RANTES、ICAM-1和γ干扰素（IFN-γ）mRNA水平。另一方面，在DBA/2小鼠中观察到的较高MIP-2和MCP-3 mRNA水平将导致巨噬细胞和中性粒细胞的更强的肺募集。此外，DBA/2小鼠在第18周和第22周表现出由大量泡沫状巨噬细胞诱导的诱导型一氧化氮合酶表达增加。这种增加是吞噬的细菌碎片的结果，是独立的IFN-γ表达，只能发挥抑菌作用。结果提示DBA/2小鼠比C57 BL/6小鼠对M.结核感染是由于支气管杆菌在活性差的泡沫状巨噬细胞内的传播。
We have used the murine model of aerosol-induced experimental tuberculosis to assess the effects of four clinical isolates and a reference strain of Mycobacterium tuberculosis on resistant C57BL/6 mice and susceptible DBA/2 mice. Histological studies and detection of 25 cytokines potentially involved in the infection were carried out. DBA/2 mice showed higher concentrations of bacilli in bronchoalveolar lavage fluid and lung tissue. Furthermore, these mice evidenced a larger granulomatous infiltration in the parenchyma due to an increased rate of emigration of infected foamy macrophages from the granulomas to the neighboring pulmonary alveolar spaces. The better control of bacillary concentrations and pulmonary infiltration observed in C57BL/6 mice from week 3 postinfection could result from their higher RANTES, ICAM-1, and gamma interferon (IFN-gamma) mRNA levels. On the other hand, the higher MIP-2 and MCP-3 mRNA levels seen in DBA/2 mice would result in stronger lung recruitment of macrophages and neutrophils. Additionally, DBA/2 mice showed increased inducible nitric oxide synthase expression, induced by the larger number of foamy macrophages, at weeks 18 and 22. This increment was a consequence of phagocytosed bacillary debris, was independent of IFN-gamma expression, and could exert only a bacteriostatic effect. The results of the study suggest that DBA/2 mice are more susceptible than C57BL/6 mice to M. tuberculosis infection due to a higher bronchial dissemination of bacilli inside poorly activated foamy macrophages.