An extracellular matrix-based mechanism of rapid neutrophil extracellular trap formation in response to Candida albicans.
An extracellular matrix-based mechanism of rapid neutrophil extracellular trap formation in response to Candida albicans.
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DOI：
10.4049/jimmunol.1202671
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发表时间：
2013-04-15
期刊：
影响因子：
--
通讯作者：
Reichner JS
中科院分区：
文献类型：
--
作者：
Byrd AS;O'Brien XM;Johnson CM;Lavigne LM;Reichner JS
中性粒细胞介导的宿主防御病原体的武器包括挤压DNA晶格和被称为中性粒细胞胞外陷阱（NETs）的杀微生物酶。受体：配体相互作用和细胞内信号传导机制负责制定NETs确定对白色念珠菌的反应。由于外渗的中性粒细胞对组织内真菌感染的宿主反应需要与ECM接触，因此本研究还发现了普遍存在的基质成分纤维连接蛋白（Fn）在NET释放中的一种新的重要调节作用。我们报道，纯化的真菌病原体相关分子模式β-葡聚糖被人类中性粒细胞识别，导致快速（≤30分钟）的同型聚集和NET释放，其机制需要Fn。单独使用时，固定的β-葡聚糖诱导活性氧（ROS）的产生，但不诱导NET的释放，而在Fn的情况下，ROS的产生被抑制，NET被挤压。NET释放到Fn + β-葡聚糖是稳健的，占细胞群总DNA的17.2±3.4%。释放依赖于CR3 （CD11b/CD18）对β-葡聚糖的识别，而不依赖于Dectin-1或ROS。NET释放的过程包括细胞内囊泡充满核物质，核物质最终被挤出。我们确定了ERK在同型聚集和NET释放中的作用。白念珠菌菌丝的NET形成也依赖于CR3对β-葡聚糖的识别，需要Fn和ERK而不需要ROS，并导致菌丝破坏。我们报道了NETosis的一种新的调控机制，其中细胞外基质是快速抗真菌反应的关键组成部分。
The armament of neutrophil-mediated host defense against pathogens includes the extrusion of a lattice of DNA and microbicidal enzymes known as Neutrophil Extracellular Traps (NETs). The receptor:ligand interactions and intracellular signaling mechanisms responsible for elaborating NETs were determined for the response to Candida albicans. Since the host response of extravasated neutrophils to mycotic infections within tissues necessitates contact with ECM, this study also identified a novel and significant regulatory role for the ubiquitous matrix component fibronectin (Fn) in NET release. We report that recognition of purified fungal pathogen-associated molecular pattern β-glucan by human neutrophils causes rapid (≤ 30 mins) homotypic aggregation and NET release by a mechanism that requires Fn. Alone, immobilized β-glucan induces reactive oxygen species (ROS) production but not NET release, whereas in the context of Fn, ROS production is suppressed and NETs are extruded. NET release to Fn + β-glucan is robust, accounting for 17.2 ± 3.4% of total DNA in the cell population. Release is dependent on β-glucan recognition by CR3 (CD11b/CD18), but not Dectin-1, or ROS. The process of NET release included filling of intracellular vesicles with nuclear material that was eventually extruded. We identify a role for ERK in homotypic aggregation and NET release. NET formation to C. albicans hyphae was also found to depend on β-glucan recognition by CR3, require Fn and ERK but not ROS, and result in hyphal destruction. We report a new regulatory mechanism of NETosis in which the extracellular matrix is a key component of the rapid anti-fungal response.
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影响因子：
8.7
作者：
Goodridge HS;Wolf AJ;Underhill DM
通讯作者：
Underhill DM
影响因子：
4.4
作者：
Lavigne, Liz M.;O'Brien, Xian M.;Reichner, Jonathan S.
通讯作者：
Reichner, Jonathan S.
影响因子：
11.8
作者：
FRASER, VJ;JONES, M;DUNAGAN, WC
通讯作者：
DUNAGAN, WC
影响因子：
82.9
作者：
Clark, Stephen R.;Ma, Adrienne C.;Kubes, Paul
通讯作者：
Kubes, Paul
DOI：
10.1083/jcb.200606027
发表时间：
2007-01-15
期刊：
The Journal of cell biology
影响因子：
--
作者：
Fuchs TA;Abed U;Goosmann C;Hurwitz R;Schulze I;Wahn V;Weinrauch Y;Brinkmann V;Zychlinsky A
通讯作者：
Zychlinsky A