Innate immune responses of airway epithelium to house dust mite are mediated through beta-glucan-dependent pathways.
Innate immune responses of airway epithelium to house dust mite are mediated through beta-glucan-dependent pathways.
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DOI：
10.1016/j.jaci.2008.12.006
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发表时间：
2009-03
影响因子：
14.2
通讯作者：
Wills-Karp, Marsha
中科院分区：
文献类型：
--
作者：
Nathan, Amy T.;Peterson, Elizabeth A.;Chakir, Jamila;Wills-Karp, Marsha
关键词：
屋尘螨（HDM）在致敏个体中诱发过敏性哮喘，尽管HDM被气道黏膜感知和识别，导致树突状细胞（DC）募集、激活和随后的th2介导反应的机制尚不清楚。我们试图确定HDM激活呼吸道上皮诱导过敏性气道反应的途径。使用人气道上皮细胞系（16HBE14o-），我们研究了暴露于HDM或其他过敏原后DC趋化因子CCL20的分泌，研究了HDM中负责诱导趋化因子释放的成分，并检查了信号通路的激活。主要发现也在人原代支气管细胞中得到证实。我们证明，气道上皮暴露于HDM导致CCL20的特异性和快速分泌，CCL20是一种未成熟树突细胞的趋化因子引诱剂。CCL20分泌的诱导具有剂量和时间依赖性，并且对HDM具有很强的特异性，因为其他过敏原如豚草花粉和蟑螂抗原不能显著诱导CCL20分泌。CCL20分泌的诱导不依赖于蛋白酶或toll样受体2/4，但有趣的是，它依赖于HDM提取物中的β-葡聚糖部分，其他β-葡聚糖竞争性抑制其分泌的能力以及β-葡聚糖酶处理HDM时破坏这些结构显著减少随后的趋化因子分泌的事实证明了这一点。综上所述，我们的研究结果描述了hdm衍生的β-葡聚糖部分特异性模式识别的新机制，该机制启动过敏性气道炎症，并且通过dc的募集，可能将气道表面的先天模式识别与适应性免疫反应联系起来。
House dust mite (HDM) induces allergic asthma in sensitized individuals, although the mechanisms by which HDM is sensed and recognized by the airway mucosa, leading to dendritic cell (DC) recruitment, activation, and subsequent TH2-mediated responses, are unknown. We sought to define the pathways by which HDM activates respiratory epithelium to induce allergic airway responses. Using a human airway epithelial cell line (16HBE14o-), we studied secretion of the DC chemokine CCL20 after exposure to HDM or other allergens, investigated components of the HDM responsible for the induction of chemokine release, and examined activation of signaling pathways. Central findings were also confirmed in primary human bronchial cells. We demonstrate that exposure of airway epithelium to HDM results in specific and rapid secretion of CCL20, a chemokine attractant for immature DCs. The induction of CCL20 secretion is dose and time dependent and quite specific to HDM because other allergens, such as ragweed pollen and cockroach antigen, fail to significantly induce CCL20 secretion. Induction of CCL20 secretion is not protease or Toll-like receptor 2/4 dependent but, interestingly, relies on β-glucan moieties within the HDM extract, as evidenced by the ability of other β-glucans to competitively inhibit its secretion and by the fact that disruption of these structures by treatment of HDM with β-glucanase significantly reduces subsequent chemokine secretion. Taken together, our results describe a novel mechanism for specific pattern recognition of HDM-derived β-glucan moieties, which initiates allergic airway inflammation and, through recruitment of DCs, might link innate pattern recognition at the airway surface with adaptive immune responses.
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Dectin-1介导β-葡聚糖的生物学作用。
DOI：
10.1084/jem.20021890
发表时间：
2003-05-05
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Brown GD;Herre J;Williams DL;Willment JA;Marshall AS;Gordon S
通讯作者：
Gordon S
DOI：
10.1084/jem.186.6.825
发表时间：
1997-09-15
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Power CA;Church DJ;Meyer A;Alouani S;Proudfoot AE;Clark-Lewis I;Sozzani S;Mantovani A;Wells TN
通讯作者：
Wells TN
影响因子：
6.1
作者：
OBRIEN, RM;THOMAS, WR
通讯作者：
THOMAS, WR
影响因子：
5.5
作者：
Sato, Tadashi;Iwabuchi, Kazuhisa;Ogawa, Hideoki
通讯作者：
Ogawa, Hideoki
DOI：
10.1165/rcmb.2002-0272oc
发表时间：
2003-11-01
影响因子：
6.4
作者：
Starner, TD;Barker, CK;McCray, PB
通讯作者：
McCray, PB