Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus.
Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus.
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DOI：
10.1038/nature25974
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发表时间：
2018-03-15
期刊：
影响因子：
64.8
通讯作者：
Brown GD
中科院分区：
文献类型：
--
作者：
Stappers MHT;Clark AE;Aimanianda V;Bidula S;Reid DM;Asamaphan P;Hardison SE;Dambuza IM;Valsecchi I;Kerscher B;Plato A;Wallace CA;Yuecel R;Hebecker B;da Glória Teixeira Sousa M;Cunha C;Liu Y;Feizi T;Brakhage AA;Kwon-Chung KJ;Gow NAR;Zanda M;Piras M;Zanato C;Jaeger M;Netea MG;van de Veerdonk FL;Lacerda JF;Campos A;Carvalho A;Willment JA;Latgé JP;Brown GD
我们对感染的抵抗力严重依赖于模式识别受体识别微生物入侵和诱导保护性免疫反应的能力。一个这样的受体家族是C型凝集素，其在抗真菌免疫中起核心作用。这些受体在识别保守的真菌细胞壁碳水化合物后激活关键效应器机制。然而，已经描述了几种其他免疫活性真菌配体，包括黑色素，其识别机制在很大程度上仍然不确定。在这里，我们确定了一个C型凝集素受体，黑色素敏感C型凝集素受体（MelLec），它通过识别1，8-二羟基萘（DHN）-黑色素的萘二醇单元在抗真菌免疫中发挥重要作用。MelLec识别烟曲霉孢子以及其他DHN黑化真菌中的黑色素，并在小鼠中广泛表达于CD 31+内皮细胞。MelLec也由共表达EpCAM的小鼠中的这些细胞的亚群表达，并且仅在肺和肝中检测到。在小鼠模型中，需要MelLec来保护免受A.烟熏。在人类中，MelLec也由骨髓细胞表达，我们鉴定了该受体的单核苷酸多态性，该受体对骨髓炎症反应产生负面影响，并显着增加干细胞移植受体对播散性曲霉菌感染的易感性。因此，MelLec是一种识别真菌上常见的免疫活性成分的受体，在小鼠和人类的抗真菌免疫保护中发挥重要作用。
Our resistance to infection is critically dependent upon the ability of pattern recognition receptors to recognise microbial invasion and induce protective immune responses. One such family of receptors are the C-type lectins, which play central roles in antifungal immunity. These receptors activate key effector mechanisms upon recognition of conserved fungal cell wall carbohydrates. However, several other immunologically active fungal ligands have been described, including melanin, whose mechanisms of recognition remain largely undefined. Here we identify a C-type lectin receptor, Melanin sensing C-type Lectin receptor (MelLec), that plays an essential role in antifungal immunity through recognition of the naphthalene-diol unit of 1,8-dihydroxynaphthalene (DHN)-melanin. MelLec recognises melanin in conidial spores of Aspergillus fumigatus, as well as other DHN-melanised fungi and is ubiquitously expressed by CD31+ endothelial cells in mice. MelLec is also expressed by a sub-population of these cells in mice that co-express EpCAM and which were detected only in the lung and liver. In mouse models, MelLec was required for protection against disseminated infection with A. fumigatus. In humans, MelLec is also expressed by myeloid cells, and we identified a single nucleotide polymorphism of this receptor that negatively affected myeloid inflammatory responses and significantly increased susceptibility of stem-cell transplant recipients to disseminated Aspergillus infections. Thus MelLec is a receptor recognising an immunologically active component commonly found on fungi and plays an essential role in protective antifungal immunity in both mice and humans.
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影响因子：
5.2
作者：
Nosanchuk JD;Stark RE;Casadevall A
通讯作者：
Casadevall A
影响因子：
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作者：
Johnson, Andrew D.;Handsaker, Robert E.;de Bakker, Paul I. W.
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de Bakker, Paul I. W.
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通讯作者：
Kullberg, Bart Jan
影响因子：
64.8
作者：
Aimanianda, Vishukumar;Bayry, Jagadeesh;Latge, Jean-Paul
通讯作者：
Latge, Jean-Paul