Dectin-2 Recognition of α-Mannans and Induction of Th17 Cell Differentiation Is Essential for Host Defense against Candida albicans
Dectin-2 Recognition of α-Mannans and Induction of Th17 Cell Differentiation Is Essential for Host Defense against Candida albicans
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DOI：
10.1016/j.immuni.2010.05.001
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发表时间：
2010-05-28
期刊：
影响因子：
32.4
通讯作者：
Iwakura, Yoichiro
中科院分区：
文献类型：
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作者：
Saijo, Shinobu;Ikeda, Satoshi;Iwakura, Yoichiro
Dectin-2(基因代码Clec4n)是一种由树突状细胞(DC)和巨噬细胞表达的C型凝集素。然而，它的功能和信号机制仍有待阐明。在这里，我们产生了Clec4n(-/-)小鼠，并表明这种分子对宿主防御白色念珠菌非常重要。Clec4n(-/-)树突状细胞几乎没有真菌α-甘露聚糖诱导的细胞因子产生。Dectin-2信号通过FCR-Gamma链和Syk-CARD9-NF-kappa B依赖的信号通路诱导细胞因子，而不涉及MAP激酶。白念珠菌的酵母形态以Dectin-2依赖的方式诱导IL-1β和IL-23的分泌。相反，菌丝形式诱导的细胞因子的产生只部分依赖于这种凝集素。酵母菌和菌丝均可诱导Th17细胞分化，主要参与Dectin-2，但不参与Dectin-1。由于IL-17A缺陷小鼠对系统性念珠菌感染高度敏感，本研究提示Dectin-2通过诱导Th17细胞分化在宿主抵抗白色念珠菌中起重要作用。
Dectin-2 (gene symbol Clec4n) is a C-type lectin expressed by dendritic cells (DCs) and macrophages. However, its functional roles and signaling mechanisms remain to be elucidated. Here, we generated Clec4n(-/-) mice and showed that this molecule is important for host defense against Candida albicans (C. albicans). Clec4n(-/-) DCs had virtually no fungal alpha-mannan-induced cytokine production. Dectin-2 signaling induced cytokines through an FcR gamma chain and Syk-CARD9-NF-kappa B-dependent signaling pathway without involvement of MAP kinases. The yeast form of C. albicans induced interleukin-1 beta (IL-1 beta) and IL-23 secretion in a Dectin-2-dependent manner. In contrast, cytokine production induced by the hyphal form was only partially dependent on this lectin. Both yeast and hyphae induced Th17 cell differentiation, in which Dectin-2, but not Dectin-1, was mainly involved. Because IL-17A-deficient mice were highly susceptible to systemic candida infection, this study suggests that Dectin-2 is important in host defense against C. albicans by inducing Th17 cell differentiation.