C-Type Lectin Receptor CD23 Is Required for Host Defense against Candida albicans and Aspergillus fumigatus Infection
C-Type Lectin Receptor CD23 Is Required for Host Defense against Candida albicans and Aspergillus fumigatus Infection
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C 型凝集素受体 CD23 是宿主防御白色念珠菌和烟曲霉感染所必需的
DOI：
10.4049/jimmunol.1800620
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发表时间：
2018-10-15
影响因子：
4.4
通讯作者：
Zhao, Xueqiang
中科院分区：
文献类型：
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作者：
Guo, Yahui;Chang, Qing;Zhao, Xueqiang
侵袭性真菌如白色念珠菌、烟曲霉和新型隐球菌的感染是日益增多的免疫功能低下和免疫缺陷患者群体的主要死亡原因之一。几种C型凝集素受体（C-type lectin receptor，CLRs），包括Dectin-1、Dectin-2、Dectin-3和Mincle，可以识别真菌表面成分并启动宿主抗真菌免疫应答。尽管如此，仍有待确定其他CLRs是否参与抗真菌免疫。我们最近的研究表明，CD 23（CLEC 4 J），一种免疫球蛋白，也是一种众所周知的B细胞表面标志物，可能具有感知C的功能。抗真菌免疫中的白念珠菌成分。然而，目前尚不清楚CD 23作为真菌模式识别受体的功能以及CD 23的抗真菌作用是否特异于C.白色或没有。在这项研究中，我们表明，CD 23可以识别α-甘露聚糖和β-葡聚糖从细胞壁的C。albicans或A.但不能识别来自隐球菌属的葡糖醛酸甘露聚糖。通过与FcRg形成复合物，CD 23可以诱导NF-κ B活化。因此，CD 23缺陷小鼠对C.白色念珠菌和A.对烟曲霉C.新生儿感染。活化的巨噬细胞中CD 23的表达对于NF-κ B的活化是关键的。CD 23缺陷导致NF-κ B依赖性基因，特别是诱导NO产生以抑制真菌感染的iNOS的表达受损。总之，我们的研究揭示了CD 23诱导的信号通路及其在抗真菌免疫中的作用，特别是对C。白色念珠菌和A.这为设计抗真菌感染的潜在治疗剂提供了分子基础。
Infection by invasive fungi, such as Candida albicans, Aspergillus fumigatus, and Cryptococcus neoformans, is one of the leading death causes for the increasing population of immunocompromised and immunodeficient patients. Several C-type lectin receptors (CLRs), including Dectin-1, -2, and -3 and Mincle can recognize fungal surface components and initiate the host antifungal immune responses. Nevertheless, it remains to be determined whether other CLRs are involved in antifungal immunity. Our recent study suggests that CD23 (CLEC4J), a CLR and also a well-known B cell surface marker, may function to sense C. albicans components in antifungal immunity. However, it is not clear how CD23 functions as a fungal pattern recognition receptor and whether the antifungal role of CD23 is specific to C. albicans or not. In this study, we show that CD23 can recognize both alpha-mannan and beta-glucan from the cell wall of C. albicans or A. fumigatus but cannot recognize glucuronoxylomannan from Cryptococcus. Through forming a complex with FcRg, CD23 can induce NF-kappa B activation. Consistently, CD23-deficient mice were highly susceptible to C. albicans and A. fumigatus but not to C. neoformans infection. The expression of CD23 in activated macrophages is critical for the activation of NF-kappa B. CD23 deficiency results in impaired expression of NF-kappa B-dependent genes, especially iNOS, which induces NO production to suppress fungal infection. Together, our studies reveal the CD23-induced signaling pathways and their roles in antifungal immunity, specifically for C. albicans and A. fumigatus, which provides the molecular basis for designing potential therapeutic agents against fungal infection.