Aspergillus fumigatus stimulates the NLRP3 inflammasome through a pathway requiring ROS production and the Syk tyrosine kinase.
Aspergillus fumigatus stimulates the NLRP3 inflammasome through a pathway requiring ROS production and the Syk tyrosine kinase.
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DOI：
10.1371/journal.pone.0010008
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发表时间：
2010-04-02
期刊：
影响因子：
3.7
通讯作者：
Ojcius DM
中科院分区：
文献类型：
--
作者：
Saïd-Sadier N;Padilla E;Langsley G;Ojcius DM
侵袭性曲霉病（IA）是一种危及生命的疾病，发生在免疫功能低下的患者感染烟曲霉后。这种真菌是继白色念珠菌之后第二常见的真菌疾病病原体。尽管如此，关于雷螨激活先天免疫系统的机制仍有待研究。我们研究了烟曲霉分生孢子和菌丝的炎症反应，特别是它们触发炎性小体激活的能力。我们的研究结果表明，与分生孢子不同，菌丝片段诱导NLRP3炎性体组装、caspase-1激活和IL-1β释放。曲霉菌丝激活单核细胞NLRP3炎性体的能力需要K+外排和ROS的产生。此外，我们的数据显示NLRP3炎性小体的激活以及il -1β的表达依赖于Syk酪氨酸激酶，而Syk酪氨酸激酶位于病原体识别受体Dectin-1的下游，这加强了Dectin-1在抗真菌感染的先天免疫应答中的重要性。此外，我们发现用皮质类固醇治疗单核细胞抑制编码IL-1β基因的转录。因此，我们的数据表明，针对烟曲霉感染的先天免疫应答涉及两个步骤的激活过程，第一个信号促进pro-IL-1β的表达和合成；第二种信号涉及syk诱导的NLRP3炎性体和caspase-1的激活，允许成熟细胞因子的加工和分泌。
Invasive aspergillosis (IA) is a life-threatening disease that occurs in immunodepressed patients when infected with Aspergillus fumigatus. This fungus is the second most-common causative agent of fungal disease after Candida albicans. Nevertheless, much remains to be learned about the mechanisms by which A. fulmigatus activates the innate immune system. We investigated the inflammatory response to conidia and hyphae of A. fumigatus and specifically, their capacity to trigger activation of an inflammasome. Our results show that in contrast to conidia, hyphal fragments induce NLRP3 inflammasome assembly, caspase-1 activation and IL-1β release from a human monocyte cell line. The ability of Aspergillus hyphae to activate the NLRP3 inflammasome in the monocytes requires K+ efflux and ROS production. In addition, our data show that NLRP3 inflammasome activation as well as pro-IL-1β expression relies on the Syk tyrosine kinase, which is downstream from the pathogen recognition receptor Dectin-1, reinforcing the importance of Dectin-1 in the innate immune response against fungal infection. Furthermore, we show that treatment of monocytes with corticosteroids inhibits transcription of the gene encoding IL-1β. Thus, our data demonstrate that the innate immune response against A. fumigatus infection involves a two step activation process, with a first signal promoting expression and synthesis of pro-IL-1β; and a second signal, involving Syk-induced activation of the NLRP3 inflammasome and caspase-1, allowing processing and secretion of the mature cytokine.
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影响因子：
16
作者：
Martinon, F;Burns, K;Tschopp, J
通讯作者：
Tschopp, J
影响因子：
39.2
作者：
GERSON, SL;TALBOT, GH;CASSILETH, PA
通讯作者：
CASSILETH, PA
影响因子：
6.7
作者：
Filler, Scott G;Sheppard, Donald C
通讯作者：
Sheppard, Donald C
DOI：
10.4049/jimmunol.0901323
发表时间：
2009-09-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Joly S;Ma N;Sadler JJ;Soll DR;Cassel SL;Sutterwala FS
通讯作者：
Sutterwala FS
影响因子：
4.8
作者：
Abdul-Sater, Ali A.;Koo, Evonne;Ojcius, David M.
通讯作者：
Ojcius, David M.