Dectin-1-induced RIPK1 and RIPK3 activation protects host against Candida albicans infection
Dectin-1-induced RIPK1 and RIPK3 activation protects host against Candida albicans infection
复制标题
Dectin-1 诱导的 RIPK1 和 RIPK3 激活可保护宿主免受白色念珠菌感染
DOI：
10.1038/s41418-019-0323-8
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发表时间：
2019-12-01
影响因子：
12.4
通讯作者：
Qian, Youcun
中科院分区：
文献类型：
--
作者：
Cao, Mengtao;Wu, Zhengxi;Qian, Youcun
坏死性凋亡是一种新近定义的程序性细胞死亡类型，其通过受体相互作用蛋白1（RIPK 1）和RIPK 3复合物的特异性信号级联来激活执行者MLKL。然而，坏死性凋亡的病理生理作用在很大程度上是未探索的。在这里，我们报告说，真菌触发骨髓细胞坏死性凋亡，这种类型的细胞死亡有助于宿主防御病原体感染。白色念珠菌及其传感器Dectin-1激活通过RIPK 1-RIPK 3-MLKL级联反应强烈诱导骨髓细胞中的坏死性凋亡。CARD 9是Dectin-1信号传导中的关键衔接子，被鉴定为桥接RIPK 1和RIPK 3复合物介导的坏死性凋亡途径。RIPK 1和RIPK 3还增强Dectin-1诱导的MLKL非依赖性炎症反应。MLKL依赖性和MLKL非依赖性途径都是宿主防御C.白色念珠菌感染因此，我们的研究证明了一种新型的宿主防御系统对真菌感染。
Necroptosis is a recently defined type of programmed cell death with the specific signaling cascade of receptor-interacting protein 1 (RIPK1) and RIPK3 complex to activate the executor MLKL. However, the pathophysiological roles of necroptosis are largely unexplored. Here, we report that fungus triggers myeloid cell necroptosis and this type of cell death contributes to host defense against the pathogen infection. Candida albicans as well as its sensor Dectin-1 activation strongly induced necroptosis in myeloid cells through the RIPK1-RIPK3-MLKL cascade. CARD9, a key adaptor in Dectin-1 signaling, was identified to bridge the RIPK1 and RIPK3 complex-mediated necroptosis pathway. RIPK1 and RIPK3 also potentiated Dectin-1-induced MLKL-independent inflammatory response. Both the MLKL-dependent and MLKL-independent pathways were required for host defense against C. albicans infection. Thus, our study demonstrates a new type of host defense system against fungal infection.