Department of Molecular Immunology, Medical Mycology Research Center, Chiba University, Chiba 260-8673, Japan.
Int Immunol. 2011 Aug;23(8):467-72. doi: 10.1093/intimm/dxr046. Epub 2011 Jun 15.
Dectin-1 and Dectin-2 are type II transmembrane proteins of the C-type lectin family with single carbohydrate recognition domains (CRDs) in their extracellular region. They are expressed mainly in dendritic cells and macrophages. Dectin-1 recognizes β-glucans with its CRD and transduces signals through its immunoreceptor tyrosine-based activation motif (ITAM)-like motif in the cytoplasmic domain, whereas Dectin-2 recognizes α-mannans and transduces its signal through association with the ITAM-containing Fc receptor γ chain. Upon ligand binding, spleen tyrosine kinase is recruited to the ITAM and activates the caspase recruitment domain family member 9 (CARD9)-nuclear factor-κB axis, resulting in the activation of various genes including those encoding pro-inflammatory cytokines. Both β-glucans and α-mannans are major cell wall components of fungi including Candida albicans and Pneumocystis carinii. Recently, it was reported that Dectin-1 is important in protection against P. carinii by inducing reactive oxygen species, whereas both Dectin-1 and Dectin-2 play important roles in defense against C. albicans by preferentially inducing T(h)17 cell differentiation. In this review, we briefly revisit the structures, ligands, signal transduction and functional roles of Dectin-1 and Dectin-2 in host defense against fungal infection.
Dectin-1 和 Dectin-2 是 C 型凝集素家族的 II 型跨膜蛋白，其细胞外区域具有单个碳水化合物识别结构域 (CRD)。它们主要在树突状细胞和巨噬细胞中表达。Dectin-1 通过其 CRD 识别β-葡聚糖，并通过其细胞质域中的免疫受体酪氨酸基激活基序 (ITAM)样基序转导信号，而 Dectin-2 识别α-甘露聚糖，并通过与含有 ITAM 的 Fc 受体γ链结合转导其信号。配体结合后，脾酪氨酸激酶被募集到 ITAM 并激活半胱天冬酶募集结构域家族成员 9 (CARD9)-核因子-κB 轴，导致包括促炎细胞因子在内的各种基因的激活。β-葡聚糖和α-甘露聚糖都是包括白色念珠菌和卡氏肺孢子虫在内的真菌的主要细胞壁成分。最近有报道称，Dectin-1 通过诱导活性氧来保护机体免受卡氏肺孢子虫的侵害，而 Dectin-1 和 Dectin-2 通过优先诱导 T(h)17 细胞分化，在防御白色念珠菌方面发挥重要作用。在这篇综述中，我们简要回顾了 Dectin-1 和 Dectin-2 在宿主防御真菌感染中的结构、配体、信号转导和功能作用。
