Activation of the pyrin inflammasome by intracellular Burkholderia cenocepacia.
Activation of the pyrin inflammasome by intracellular Burkholderia cenocepacia.
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DOI：
10.4049/jimmunol.1102272
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发表时间：
2012-04-01
期刊：
影响因子：
--
通讯作者：
Amer AO
中科院分区：
文献类型：
--
作者：
Gavrilin MA;Abdelaziz DH;Mostafa M;Abdulrahman BA;Grandhi J;Akhter A;Abu Khweek A;Aubert DF;Valvano MA;Wewers MD;Amer AO
新洋葱伯克霍尔德菌是一种机会致病菌，可引起囊性纤维化患者慢性感染并诱导进行性呼吸道炎症。单核细胞对细菌的识别通常导致半胱天冬酶-1的活化和IL-1β（一种主要的促炎细胞因子）的加工。在这项研究中，我们报告说，人类pyrin需要检测细胞内B。新洋葱病导致IL-1β加工和释放。这种炎症反应涉及宿主衔接分子ASC和细菌VI型分泌系统（T6 SS）。用B感染稳定表达针对pyrin或YFP-pyrin和ASC（YFP-ASC）的小干扰RNA的人单核细胞和THP-1细胞。并分析炎性小体活化。B。cenocepacia有效激活单核细胞和THP-1中的炎性小体和IL-1β释放。抑制单核细胞和THP-1细胞中的pyrin水平可减少响应于B的caspase-1活化和IL-1β释放。新洋葱挑战赛。相反，pyrin或ASC的过表达诱导了对B的强IL-1β应答。cenocepacia，其与增强的宿主细胞死亡相关。在感染了B的T6 SS缺陷突变体的细胞中，炎性小体活化显著降低。这表明炎症反应可能是由尚未表征的T6 SS效应物诱导的。总之，据我们所知，我们第一次证明了在感染B的人单核细胞中。在cenocepacia中，pyrin与半胱天冬酶-1和ASC缔合，形成上调单核细胞IL-1β加工和释放的炎性体。
Burkholderia cenocepacia is an opportunistic pathogen that causes chronic infection and induces progressive respiratory inflammation in cystic fibrosis patients. Recognition of bacteria by mononuclear cells generally results in the activation of caspase-1 and processing of IL-1β, a major proinflammatory cytokine. In this study, we report that human pyrin is required to detect intracellular B. cenocepacia leading to IL-1β processing and release. This inflammatory response involves the host adapter molecule ASC and the bacterial type VI secretion system (T6SS). Human monocytes and THP-1 cells stably expressing either small interfering RNA against pyrin or YFP–pyrin and ASC (YFP–ASC) were infected with B. cenocepacia and analyzed for inflammasome activation. B. cenocepacia efficiently activates the inflammasome and IL-1β release in monocytes and THP-1. Suppression of pyrin levels in monocytes and THP-1 cells reduced caspase-1 activation and IL-1β release in response to B. cenocepacia challenge. In contrast, overexpression of pyrin or ASC induced a robust IL-1β response to B. cenocepacia, which correlated with enhanced host cell death. Inflammasome activation was significantly reduced in cells infected with T6SS-defective mutants of B. cenocepacia, suggesting that the inflammatory reaction is likely induced by an as yet uncharacterized effector(s) of the T6SS. Together, we show for the first time, to our knowledge, that in human mononuclear cells infected with B. cenocepacia, pyrin associates with caspase-1 and ASC forming an inflammasome that upregulates mononuclear cell IL-1β processing and release.
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DOI：
10.1074/jbc.m110.197681
发表时间：
2011-02-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Abdelaziz DH;Gavrilin MA;Akhter A;Caution K;Kotrange S;Khweek AA;Abdulrahman BA;Grandhi J;Hassan ZA;Marsh C;Wewers MD;Amer AO
通讯作者：
Amer AO
DOI：
10.4049/jimmunol.1003111
发表时间：
2011-02-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Davis BK;Roberts RA;Huang MT;Willingham SB;Conti BJ;Brickey WJ;Barker BR;Kwan M;Taxman DJ;Accavitti-Loper MA;Duncan JA;Ting JP
通讯作者：
Ting JP
DOI：
10.4049/jimmunol.1003034
发表时间：
2011-07-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Cremer TJ;Shah P;Cormet-Boyaka E;Valvano MA;Butchar JP;Tridandapani S
通讯作者：
Tridandapani S
影响因子：
30.5
作者：
Buerckstuemmer, Tilmann;Baumann, Christoph;Superti-Furga, Giulio
通讯作者：
Superti-Furga, Giulio
DOI：
10.1073/pnas.0504271103
发表时间：
2006-01-03
影响因子：
11.1
作者：
Gavrilin, MA;Bouakl, IJ;Wewers, MD
通讯作者：
Wewers, MD