Dendritic cell interaction with Candida albicans critically depends on N-linked mannan
Dendritic cell interaction with Candida albicans critically depends on N-linked mannan
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DOI：
10.1074/jbc.m709334200
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发表时间：
2008-07-18
影响因子：
4.8
通讯作者：
Figdor, Carl G.
中科院分区：
文献类型：
--
作者：
Cambi, Alessandra;Netea, Mihai G.;Figdor, Carl G.
真菌白色念珠菌是免疫功能低下宿主真菌感染的最常见原因。念珠菌与免疫细胞受体之间的初始相互作用知之甚少，因为缺乏结构水平上的详细表征。抗原呈递树突状细胞（dc）战略性地位于粘膜表面和皮肤中，可能在抗念珠菌保护性免疫中发挥重要作用。然而，各种与念珠菌相关的分子模式及其对抗受体对DC功能的贡献仍然未知。在这里，我们证明了两种c型凝集素DC-SIGN和巨噬细胞甘露糖受体特异性地介导白色念珠菌与人类dc的结合和内化。此外，通过将一系列白色念珠菌糖基化突变体与受体特异性阻断和细胞因子产生试验相结合，我们确定n -连接甘露聚糖而不是o -连接或磷酸甘露聚糖是真菌碳水化合物结构，可被人类dc上的c型凝集素特异性识别，并直接影响促炎细胞因子IL-6的产生。更好地了解c型凝集素的碳水化合物识别谱将最终为开发针对特定真菌细胞壁抗原的新药提供相关信息。
The fungus Candida albicans is the most common cause of mycotic infections in immunocompromised hosts. Little is known about the initial interactions between Candida and immune cell receptors, because a detailed characterization at the structural level is lacking. Antigen-presenting dendritic cells (DCs), strategically located at mucosal surfaces and in the skin, may play an important role in anti-Candida protective immunity. However, the contribution of the various Candida-associated molecular patterns and their counter-receptors to DC function remains unknown. Here, we demonstrate that two C-type lectins, DC-SIGN and the macrophage mannose receptor, specifically mediate C. albicans binding and internalization by human DCs. Moreover, by combining a range of C. albicans glycosylation mutants with receptor-specific blocking and cytokine production assays, we determined that N-linked mannan but not O-linked or phosphomannan is the fungal carbohydrate structure specifically recognized by both C-type lectins on human DCs and directly influences the production of the proinflammatory cytokine IL-6. Better insight in the carbohydrate recognition profile of C-type lectins will ultimately provide relevant information for the development of new drugs targeting specific fungal cell wall antigens.