Invariant natural killer T cells recognize a fungal glycosphingolipid that can induce airway hyperreactivity.
Invariant natural killer T cells recognize a fungal glycosphingolipid that can induce airway hyperreactivity.
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烟曲霉是一种腐生真菌，在环境中无处不在，通常与人类的过敏致敏和严重哮喘相关。尽管烟曲霉可被多种微生物模式识别受体识别，但我们鉴定并合成了一种烟曲霉鞘糖脂——曲酰胺B，它在体外以一种依赖CD1d、不依赖MyD88和dectin - 1的方式直接激活不变自然杀伤T（iNKT）细胞。此外，当曲酰胺B加载到CD1d上时，可直接对iNKT细胞进行染色，并且足以激活iNKT细胞。在体内，曲酰胺B以一种依赖白细胞介素 - 33 - ST2的方式激活肺部iNKT细胞，从而迅速诱导气道高反应性，这是哮喘的一个主要特征。因此，曲酰胺B是第一种被发现可直接激活iNKT细胞的真菌糖脂。这些结果将iNKT细胞可直接检测的微生物范围扩展到了真菌界，并可能解释了烟曲霉在导致人类严重慢性呼吸道疾病方面的有效性。
Aspergillus fumigatusis a saprophytic fungus that is ubiquitous in the environment and commonly associated with allergic sensitization and severe asthma in humans. Although A. fumigatus is recognized by multiple microbial pattern recognition receptors, we identified and synthesized an A. fumigatus glycosphingolipid, asperamide B, that directly activated invariant natural killer T (iNKT) cells in vitro in a CD1d-restricted, MyD88- and dectin-1-independent fashion. Moreover, asperamide B, when loaded into CD1d, directly stained, and was sufficient to activate, iNKT cells. In vivo, asperamide B rapidly induced airway hyperreactivity, a cardinal feature of asthma, by activating pulmonary iNKT cells in an IL-33-ST2-dependent fashion. Asperamide B is thus the first fungal glycolipid found to directly activate iNKT cells. These results extend the range of microorganisms that can be directly detected by iNKT cells to the Kingdom of Fungi, and may explain the effectiveness of A. fumigatus in causing severe chronic respiratory diseases in humans.
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影响因子：
14.2
作者：
Broadfield, E;McKeever, TM;Britton, J
通讯作者：
Britton, J
DOI：
10.1084/jem.20100793
发表时间：
2011-03-14
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Barrett NA;Rahman OM;Fernandez JM;Parsons MW;Xing W;Austen KF;Kanaoka Y
通讯作者：
Kanaoka Y
DOI：
10.1016/j.jaci.2010.10.048
发表时间：
2011-02
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Huang YJ;Nelson CE;Brodie EL;Desantis TZ;Baek MS;Liu J;Woyke T;Allgaier M;Bristow J;Wiener-Kronish JP;Sutherland ER;King TS;Icitovic N;Martin RJ;Calhoun WJ;Castro M;Denlinger LC;Dimango E;Kraft M;Peters SP;Wasserman SI;Wechsler ME;Boushey HA;Lynch SV;National Heart, Lung, and Blood Institute's Asthma Clinical Research Network
通讯作者：
National Heart, Lung, and Blood Institute's Asthma Clinical Research Network
影响因子：
32.4
作者：
Halim, Timotheus Y. F.;Krauss, Ramona H.;Takei, Fumio
通讯作者：
Takei, Fumio
DOI：
10.1164/rccm.201001-0087oc
发表时间：
2010-12-01
影响因子：
24.7
作者：
Fairs, Abbie;Agbetile, Joshua;Pashley, Catherine H.
通讯作者：
Pashley, Catherine H.