Mechanistic Insights into the Role of C-Type Lectin Receptor/CARD9 Signaling in Human Antifungal Immunity.
Mechanistic Insights into the Role of C-Type Lectin Receptor/CARD9 Signaling in Human Antifungal Immunity.
复制标题
对C型凝集素受体/Card9信号在人类抗真菌免疫中的作用的机械洞察力。
DOI：
10.3389/fcimb.2016.00039
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发表时间：
2016
影响因子：
5.7
通讯作者：
Lionakis MS
中科院分区：
文献类型：
--
作者：
Drummond RA;Lionakis MS
人CARD 9缺陷是由基因CARD 9中的双等位基因突变引起的常染色体隐性原发性免疫缺陷病症，所述基因CARD 9编码在许多C型凝集素受体（CLR）下游发现的信号蛋白。CLR包括一个大家族的先天性识别受体，主要由骨髓和上皮细胞表达，其结合真菌碳水化合物并启动抗真菌免疫应答。因此，人CARD 9缺陷与主要局限于皮肤和皮下组织、粘膜表面和/或中枢神经系统（CNS）的持续性和严重真菌感染的自发发展相关。在过去的3年中，已经报道了超过15种错义和无义CARD 9突变，其与由多种真菌生物体引起的广谱真菌感染的发展相关。CARD 9针对这些真菌感染提供器官特异性保护的机制现在正在出现。在这篇综述中，我们总结了最近的免疫学和临床进展，提供了显着的机制洞察人类CARD 9缺陷的发病机制。我们还讨论了CARD 9偶联受体（Dectin-1，Dectin-2）和CARD 9结合伴侣（MALT 1，BCL 10）中的基因突变如何影响相对于CARD 9缺陷的人类抗真菌免疫力，我们强调了值得进一步研究的主要研究问题。
Human CARD9 deficiency is an autosomal recessive primary immunodeficiency disorder caused by biallelic mutations in the gene CARD9, which encodes a signaling protein that is found downstream of many C-type lectin receptors (CLRs). CLRs encompass a large family of innate recognition receptors, expressed predominantly by myeloid and epithelial cells, which bind fungal carbohydrates and initiate antifungal immune responses. Accordingly, human CARD9 deficiency is associated with the spontaneous development of persistent and severe fungal infections that primarily localize to the skin and subcutaneous tissue, mucosal surfaces and/or central nervous system (CNS). In the last 3 years, more than 15 missense and nonsense CARD9 mutations have been reported which associate with the development of a wide spectrum of fungal infections caused by a variety of fungal organisms. The mechanisms by which CARD9 provides organ-specific protection against these fungal infections are now emerging. In this review, we summarize recent immunological and clinical advances that have provided significant mechanistic insights into the pathogenesis of human CARD9 deficiency. We also discuss how genetic mutations in CARD9-coupled receptors (Dectin-1, Dectin-2) and CARD9-binding partners (MALT1, BCL10) affect human antifungal immunity relative to CARD9 deficiency, and we highlight major understudied research questions which merit future investigation.