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首页> 外文期刊>Infection and immunity >Genetically Determined Disparate Innate and Adaptive Cell-Mediated Immune Responses to Pulmonary Mycobacterium bovis BCG Infection in C57BL/6 and BALB/c Mice
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Genetically Determined Disparate Innate and Adaptive Cell-Mediated Immune Responses to Pulmonary Mycobacterium bovis BCG Infection in C57BL/6 and BALB/c Mice

机译：遗传确定的不同的先天性和适应性细胞介导的C57BL / 6和BALB / c小鼠对牛分枝杆菌BCG感染的免疫反应

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The current study was designed to investigate the impact of genetic heterogeneity on host immune responses to pulmonary intracellular infection by using two mouse strains of distinct genetic background, C57BL/6 and BALB/c mice, and a model intracellular pathogen,Mycobacterium bovis BCG. Upon infection, compared to C57BL/6 mice, BALB/c mice developed an earlier response of interleukin 12 (IL-12), gamma interferon (IFN-γ), tumor necrosis factor alpha, and macrophage chemoattractive protein 1, and greater neutrophilic influx to the lung by days 7 and 14. However, the level of these cytokines at days 27, 43, and 71 was much lower in BALB/c mice than in C57BL/6 mice. The magnitude of cellular responses was also much lower in the lung of BALB/c mice around day 27. Histologically, while C57BL/6 mice developed lymphocytic granulomas, BALB/c mice displayed atypical granulomas in the lung. Of importance, the level of type 2 cytokines IL-4 and IL-10 remained low and similar in the lung of both C57BL/6 and BALB/c mice throughout. Furthermore, lymphocytes isolated from systemic and local lymphoid tissues of infected BALB/c mice demonstrated a markedly lower antigen-specific IFN-γ recall response. While the number of mycobacterial bacilli recovered from both the lung and spleen of BALB/c mice was similar to that in C57BL/6 mice at day 14, it was higher than that in C57BL/6 mice at day 43. However, it was eventually leveled off to that in C57BL/6 counterparts later. These results suggest the following: (i) genetic heterogeneity can lead to differential innate and adaptive cell-mediated immune responses to primary pulmonary mycobacterial infection; (ii) it is the level of adaptive, but not innate, immune response that is critical to host resistance; and (iii) a lower type 1 immune response in BALB/c mice is not accompanied by a heightened type 2 response during pulmonary mycobacterial infection.
机译：本研究旨在通过使用两种具有不同遗传背景的小鼠品系C57BL / 6和BALB / c小鼠品系以及模型细胞内病原体牛分枝杆菌来研究遗传异质性对宿主对肺部细胞内感染的免疫反应的影响 BCG。感染后，与C57BL / 6小鼠相比，BALB / c小鼠对白介素12（IL-12），γ干扰素（IFN-γ），肿瘤坏死因子α和巨噬细胞趋化蛋白1的反应更早，并且嗜中性粒细胞增多在第7和14天时，这些细胞因子的水平显着降低。然而，在BALB / c小鼠中，这些细胞因子的水平在27、43和71天时要比C57BL / 6小鼠低得多。在第27天左右，BALB / c小鼠的肺细胞反应程度也低得多。从组织学上讲，虽然C57BL / 6小鼠发展了淋巴细胞肉芽肿，但BALB / c小鼠在肺中表现出非典型肉芽肿。重要的是，整个C57BL / 6和BALB / c小鼠的肺中2型细胞因子IL-4和IL-10的水平仍然很低，并且相似。此外，从感染的BALB / c小鼠的全身和局部淋巴组织中分离的淋巴细胞显示出明显更低的抗原特异性IFN-γ召回反应。虽然从第14天的BALB / c小鼠的肺和脾中回收的分枝杆菌的数量与C57BL / 6小鼠的相似，但高于第43天的C57BL / 6小鼠。但是最终后来与C57BL / 6同行的水平持平。这些结果表明：（i）遗传异质性可导致对原发性肺分支杆菌感染的先天性和适应性细胞介导的免疫反应不同; （ii）适应性而非先天性免疫应答的水平对宿主抵抗力至关重要; （iii）在肺分枝杆菌感染过程中，BALB / c小鼠的1型免疫应答较低，而2型免疫应答并未升高。

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