C-type Lectin
C-type Lectin
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2022
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通讯作者：
J. Reedy;Arianne J. Crossen;Paige E. Negoro;Hannah E. Brown;A. Rebecca;Ward;Diego A. Vargas Blanco;Kyle D. Timmer;Michael K. Mansour;Marcel Wüthrich;T. Fontaine;J. Latgé;J. Vyas
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作者：
J. Reedy;Arianne J. Crossen;Paige E. Negoro;Hannah E. Brown;A. Rebecca;Ward;Diego A. Vargas Blanco;Kyle D. Timmer;Michael K. Mansour;Marcel Wüthrich;T. Fontaine;J. Latgé;J. Vyas
烟曲霉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会导致显著的死亡率。在患者血清和支气管肺泡灌洗液中检测曲霉菌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先天免疫系统识别缺乏基本的了解。半乳甘露聚糖由具有31个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，我们利用由纯化的曲霉半乳甘露聚糖组成的真菌样颗粒33来鉴定负责结合这种真菌碳水化合物的C型凝集素宿主受体34。我们确定了35曲霉半乳甘露聚糖和C型凝集素受体Dectin-2之间的新的相互作用。我们证明了半乳甘露聚糖与Dectin-2结合并诱导Dectin-2依赖性信号传导，包括脾酪氨酸激酶的活化和有效的TNF α产生。Dectin-2的缺乏增加了中性粒细胞38向肺的募集，但在肺曲霉病小鼠模型中对存活率不利。我们的结果确定了半乳甘露聚糖与Dectin-2和40之间的新型相互作用，表明Dectin-2是曲霉半乳甘露聚糖的受体，可导致pro- 41炎症反应。42 45 46 47凝集素受体Dectin-2。证明半乳甘露聚糖诱导巨噬细胞中的Dectin-2促炎信号传导。甘露聚糖a-1，2-连接的甘露四糖B-1，5-连接的生命周期。B-1，3-形态动力学细胞（PBMC）可溶性半乳甘露聚糖LPS诱导的细胞因子半乳甘露聚糖Th 2/Th 17免疫Dectin-2在曲霉半乳甘露聚糖天然免疫识别中的新的重要作用。最近在Dectin-2中发现的导致对曲霉菌的反应性降低的病例也证明了Dectin-2在介导浆细胞样树突状细胞（pDC）A中的作用。
: 25 Aspergillus fumigatus is a ubiquitous environmental mold that causes significant mortality 26 particularly amongst immunocompromised patients. The detection of the Aspergillus- derived 27 carbohydrate galactomannan in patient sera and bronchoalveolar lavage fluid is the major 28 biomarker used to detect A. fumigatus infection in clinical medicine. Despite the clinical relevance 29 of this carbohydrate, we lack a fundamental understanding of how galactomannan is recognized 30 by the innate immune system. Galactomannan is composed of a linear mannan backbone with 31 galactofuranose sidechains and is found both attached to the cell surface of Aspergillus and as a 32 soluble carbohydrate in the extracellular milieu. In this study, we utilized fungal-like particles 33 composed of purified Aspergillus galactomannan to identify a C-type lectin host receptor 34 responsible for binding this fungal carbohydrate. We identified a novel interaction between 35 Aspergillus galactomannan and the C-type lectin receptor Dectin-2. We demonstrate that 36 galactomannan bound to Dectin-2 and induced Dectin-2 dependent signaling including activation 37 of spleen tyrosine kinase and potent TNFa production. Deficiency of Dectin-2 increased neutrophil 38 recruitment to the lungs but was dispensable for survival in a mouse model of pulmonary 39 aspergillosis. Our results identify a novel interaction between galactomannan and Dectin-2 and 40 demonstrate that Dectin-2 is a receptor for Aspergillus galactomannan which leads to a pro- 41 inflammatory response. 42 45 46 47 lectin receptor Dectin-2. demonstrate galactomannan induces Dectin-2 proinflammatory signaling in macrophages. mannan a-1,2-linked mannotetraose b-1,5-linked lifecycle. b-1,3- morphology kinetics cells (PBMCs) soluble galactomannan LPS-induced cytokine an galactomannan Th2/Th17 immunity novel important role for Dectin-2 in innate immune recognition of Aspergillus galactomannan. A recent case a found a in Dectin-2 that led to decreased responsiveness to Aspergillus Previous also demonstrated a role for Dectin-2 in mediating plasmacytoid dendritic (pDC) A.