Borrelia species induce inflammasome activation and IL-17 production through a caspase-1-dependent mechanism.
Borrelia species induce inflammasome activation and IL-17 production through a caspase-1-dependent mechanism.
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DOI：
10.1002/eji.201040385
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发表时间：
2011-01
影响因子：
5.4
通讯作者：
Joosten, Leo A. B.
中科院分区：
文献类型：
--
作者：
Oosting, Marije;van de Veerdonk, Frank L.;Kanneganti, Thirumala-Devi;Sturm, Patrick;Verschueren, Ineke;Berende, Anneleen;van der Meer, Jos W. M.;Kullberg, Bart-Jan;Netea, Mihai G.;Joosten, Leo A. B.
伯氏疏螺旋体引起莱姆病，可导致严重的临床症状，如多发性关节炎症和神经疾病。干扰素-γ和IL-17被认为在宿主对疏螺旋体的免疫防御和莱姆病的免疫病理中发挥重要作用。Caspase-1依赖的细胞因子IL-1β与产生IL-17的T细胞有关，而Caspase-1介导的IL-18对干扰素-γ的产生至关重要。在这项研究中，我们通过使用基因敲除小鼠展示了炎症体激活的caspase-1对伯氏杆菌细胞因子反应的调节作用。经疏螺旋体刺激后，Caspase-1缺陷细胞产生的干扰素-γ和IL-17显著减少。IL-1β的缺乏是导致IL-17产生缺陷的原因，而IL-18是产生干扰素-γ的关键。依赖Caspase-1的IL-33在疏螺旋体诱导的IL-1β、干扰素-γ和IL-17的产生中没有作用。总之，我们首次描述了依赖炎症体的caspase-1激活细胞因子在调节疏螺旋体诱导的IL-17产生中的作用。由于IL-17参与了慢性莱姆病的发病机制，这些数据提示，caspase-1靶向可能是治疗晚期莱姆病并发症的一种新的免疫调节策略。
Borrelia burgdorferi spirochetes cause Lyme Disease, which can result in severe clinical symptoms such as multiple joint inflammation and neurological disorders. IFN-γ and IL-17 have been suggested to play an important role in the host defense against Borrelia, and in the immunopathology of Lyme Disease. The caspase-1 dependent cytokine IL-1β has been linked to the generation of IL-17-producing T cells, whereas caspase-1-mediated IL-18 is crucial for IFN-γ production. In this study, we show by using knockout mice the role of inflammasome-activated caspase-1 for the regulation of cytokine responses by B. burgdorferi. Caspase-1 deficient cells showed significantly less IFN-γ and IL-17 production after Borrelia stimulation. A lack of IL-1β was responsible for the defective IL-17 production, whereas IL-18 was crucial for the IFN-γ production. Caspase-1 dependent IL-33 played no role in the Borrelia-induced production of IL-1β, IFN-γ or IL-17. In conclusion, we describe for the first time the role of the inflammasome-dependent caspase-1 activation of cytokines for the regulation of IL-17 production induced by Borrelia spp. As IL-17 has been implicated in the pathogenesis of chronic Lyme disease, these data suggests that caspase-1 targeting may represent a new immunomodulatory strategy for the treatment of complications of late stage Lyme disease.
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DOI：
10.1073/pnas.0812690106
发表时间：
2009-06-02
影响因子：
11.1
作者：
Cayrol, Corinne;Girard, Jean-Philippe
通讯作者：
Girard, Jean-Philippe
影响因子：
30.5
作者：
Acosta-Rodriguez, Eva V.;Napolitani, Giorgio;Sallusto, Federica
通讯作者：
Sallusto, Federica
影响因子：
3.1
作者：
Brown, CR;Reiner, SL
通讯作者：
Reiner, SL
影响因子：
3.8
作者：
Chabaud, M;Garnero, P;Miossec, P
通讯作者：
Miossec, P
DOI：
10.1016/j.bbrc.2009.12.107
发表时间：
2010-01-15
影响因子：
3.1
作者：
Ali, Shafaqat;Nguyen, Dang Quan;Martin, Michael Uwe
通讯作者：
Martin, Michael Uwe