The C-Type Lectin Receptor Dectin-2 Is a Receptor for Aspergillus fumigatus Galactomannan.
The C-Type Lectin Receptor Dectin-2 Is a Receptor for Aspergillus fumigatus Galactomannan.
复制标题
作者：
烟曲霉菌是一种普遍存在的环境霉菌，特别是在免疫功能低下的患者中导致显著的死亡率。在患者血清和支气管肺泡灌洗液中检测到的曲霉衍生的碳水化合物半乳甘露聚糖是用于检测A.临床医学中的烟曲霉感染。尽管这种碳水化合物具有临床意义，但我们对半乳甘露聚糖如何被免疫系统识别及其后果缺乏基本了解。半乳甘露聚糖由具有半乳呋喃糖侧链的线性甘露聚糖主链组成，并且发现其既附着于曲霉属的细胞表面，又作为细胞外环境中的可溶性碳水化合物。在这项研究中，我们利用高度纯化的曲霉半乳甘露聚糖组成的真菌样颗粒，以确定这种真菌碳水化合物的C型凝集素宿主受体。我们确定了曲霉半乳甘露聚糖和C型凝集素受体Dectin-2之间的一种新的和特异性的相互作用。我们证明半乳甘露聚糖结合Dectin-2并诱导Dectin-2依赖性信号传导，包括脾酪氨酸激酶激活、基因转录和肿瘤坏死因子α（TNF-α）产生。Dectin-2的缺乏增加了免疫细胞向肺部的募集，但在肺曲霉病小鼠模型中对存活率不利。我们的研究结果确定了半乳甘露聚糖和Dectin-2之间的一种新的相互作用，并证明Dectin-2是半乳甘露聚糖的受体，这导致了肺部的促炎免疫反应。
Aspergillus fumigatus is a ubiquitous environmental mold that causes significant mortality particularly among immunocompromised patients. The detection of the Aspergillus-derived carbohydrate galactomannan in patient serum and bronchoalveolar lavage fluid is the major biomarker used to detect A. fumigatus infection in clinical medicine. Despite the clinical relevance of this carbohydrate, we lack a fundamental understanding of how galactomannan is recognized by the immune system and its consequences. Galactomannan is composed of a linear mannan backbone with galactofuranose sidechains and is found both attached to the cell surface of Aspergillus and as a soluble carbohydrate in the extracellular milieu. In this study, we utilized fungal-like particles composed of highly purified Aspergillus galactomannan to identify a C-type lectin host receptor for this fungal carbohydrate. We identified a novel and specific interaction between Aspergillus galactomannan and the C-type lectin receptor Dectin-2. We demonstrate that galactomannan bound to Dectin-2 and induced Dectin-2-dependent signaling, including activation of spleen tyrosine kinase, gene transcription, and tumor necrosis factor alpha (TNF-α) production. Deficiency of Dectin-2 increased immune cell recruitment to the lungs but was dispensable for survival in a mouse model of pulmonary aspergillosis. Our results identify a novel interaction between galactomannan and Dectin-2 and demonstrate that Dectin-2 is a receptor for galactomannan, which leads to a proinflammatory immune response in the lung.
登录
查看更多内容
DOI：
10.1093/infdis/jiab145
发表时间：
2021-10-13
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Griffiths JS;White PL;Czubala MA;Simonazzi E;Bruno M;Thompson A;Rizkallah PJ;Gurney M;da Fonseca DM;Naglik JR;Ingram W;Wilson K;van de Veerdonk FL;Barnes R;Taylor PR;Orr SJ
通讯作者：
Orr SJ
影响因子：
6.7
作者：
Gravelat FN;Beauvais A;Liu H;Lee MJ;Snarr BD;Chen D;Xu W;Kravtsov I;Hoareau CM;Vanier G;Urb M;Campoli P;Al Abdallah Q;Lehoux M;Chabot JC;Ouimet MC;Baptista SD;Fritz JH;Nierman WC;Latgé JP;Mitchell AP;Filler SG;Fontaine T;Sheppard DC
通讯作者：
Sheppard DC
影响因子：
5.8
作者：
Chai, Louis Y. A.;Vonk, Alieke G.;Netea, Mihai G.
通讯作者：
Netea, Mihai G.
影响因子：
4.9
作者：
Bowman, JC;Abruzzo, GK;Douglas, CM
通讯作者：
Douglas, CM
影响因子：
3.1
作者：
Ibrahim-Granet, O;Philippe, B;Latgé, JP
通讯作者：
Latgé, JP