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首页> 外文期刊>Immunology: An Official Journal of the British Society for Immunology >Mice genetically inactivated in interleukin-17a receptor are defective in long-term control of mycobacterium tuberculosis infection
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Mice genetically inactivated in interleukin-17a receptor are defective in long-term control of mycobacterium tuberculosis infection

机译：白细胞介素17a受体基因失活的小鼠在结核分枝杆菌感染的长期控制中存在缺陷

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Summary: Interleukin-17A (IL-17A), a pro-inflammatory cytokine acting on neutrophil recruitment, is known to play an important role during Mycobacterium tuberculosis infection, but the role of IL-17A receptor signalling in immune defence against this intracellular pathogen remains poorly documented. Here we have analysed this signalling using C57BL/6 mice genetically inactivated in the IL-17 receptor A subunit (IL-17RA-/-). Although early after infection bacterial growth was controlled to the same extent as in wild-type mice, IL-17RA-/- mice were defective in exerting long-term control of M. tuberculosis infection, as demonstrated by a progressively increasing pulmonary bacterial burden and shortened survival time. Compared with infected wild-type mice, IL-17RA-/- mice showed impaired recruitment of neutrophils to the lungs at the early but not the late stage of infection. Pulmonary tumour necrosis factor-α, IL-6 and particularly IL-10 levels were decreased in the absence of IL-17RA signalling, whereas IL-1β was increased. CD4+-mediated and γδ-mediated IL-17A production was dramatically increased in IL-17RA-/- mice (confirming part of their phenotype), whereas production of interferon-γ and expression of the bactericidal enzyme inducible nitric oxide synthase were not affected. Collectively, our data suggest that early but not late neutrophil recruitment is essential for IL-17A-mediated long-term control of M. tuberculosis infection and that a functional interferon-γ response is not sufficient to control M. tuberculosis growth when the IL-17RA pathway is deficient. As treatment of auto-immune diseases with anti-IL-17A antibodies is actually being tested in clinical studies, our data suggest that caution should be taken with respect to possible reactivation of tuberculosis.
机译：简介：白介素17A（IL-17A）是一种作用于嗜中性粒细胞募集的促炎细胞因子，在结核分枝杆菌感染期间起着重要作用，但IL-17A受体信号传导在抵抗这种细胞内病原体的免疫防御中仍然发挥作用记录不足。在这里，我们使用在IL-17受体A亚基（IL-17RA-/-）中基因失活的C57BL / 6小鼠分析了这种信号传导。尽管感染后早期细菌的生长受到的控制与野生型小鼠相同，但是IL-17RA-/-小鼠无法长期控制结核分枝杆菌感染，这通过逐渐增加的肺部细菌负担和缩短了生存时间。与感染的野生型小鼠相比，IL-17RA-/-小鼠在感染的早期而非晚期表现出中性粒细胞向肺的募集受损。在没有IL-17RA信号的情况下，肺肿瘤坏死因子-α，IL-6尤其是IL-10的水平降低，而IL-1β升高。在IL-17RA-/-小鼠中CD4 +介导的和γδ介导的IL-17A的产生显着增加（证实了其部分表型），而干扰素-γ的产生和杀菌酶诱导型一氧化氮合酶的表达没有受到影响。总体而言，我们的数据表明，早期但不是晚期募集中性粒细胞对于IL-17A介导的结核分枝杆菌感染的长期控制至关重要，并且当IL-A介导时，功能性干扰素-γ反应不足以控制结核分枝杆菌的生长。 17RA途径不足。由于实际上已经在临床研究中测试了使用抗IL-17A抗体治疗自身免疫性疾病的能力，因此我们的数据表明，在结核病可能重新激活方面应谨慎行事。

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