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NK cell recognition of Candida glabrata throughbinding of NKp46 and NCR1 to fungal ligands Epa1 Epa6 and Epa7

机译:NK细胞对光滑念珠菌的识别NKp46和NCR1与真菌配体Epa1Epa6和Epa7的结合

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摘要

Natural Killer (NK) cells form an important arm of the innate immune system and function to combat a wide range of invading pathogens, ranging from viruses to bacteria. However, the means by which NK cells accomplish recognition of pathogens with a limited repertoire of receptors remains largely unknown. In the current study, we describe the recognition of an emerging fungal pathogen, Candida glabrata, by the human NK cytotoxic receptor NKp46 and its mouse ortholog NCR1. Using NCR1 knockout mice, we observed that this receptor-mediated recognition was crucial for controlling C. glabrata infection in vitro and in vivo. Finally, we delineated the fungal ligands to be the C. glabrata adhesins Epa1, Epa6 and Epa7 and demonstrate that clearance of systemic C. glabrata infections in vivo depends on their recognition by NCR1. As NKp46 and NCR1 have been previously shown to bind viral adhesion receptors, we speculate that NKp46/NCR1 may be a novel type of pattern recognition receptor.
机译:天然杀伤细胞(NK)构成先天免疫系统的重要组成部分,并具有抗击各种入侵病原体的功能,从病毒到细菌。但是,NK细胞通过有限的受体库完成病原体识别的方法仍然是未知的。在当前的研究中,我们描述了人类NK细胞毒性受体NKp46及其小鼠直系同源物NCR1对一种新兴真菌病原体光滑念珠菌的识别。使用NCR1基因敲除小鼠,我们观察到这种受体介导的识别对于在体外和体内控制光滑念珠菌感染至关重要。最后,我们将真菌配体划定为光滑念珠菌粘附蛋白Epa1,Epa6和Epa7,并证明体内系统性光滑念珠菌感染的清除取决于它们对NCR1的识别。由于先前已显示NKp46和NCR1可以结合病毒粘附受体,因此我们推测NKp46 / NCR1可能是新型的模式识别受体。

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