NLRP3炎性小体在宿主抵御人类真菌病原体白色念珠菌的过程中发挥着重要作用。
An essential role for the NLRP3 inflammasome in host defense against the human fungal pathogen Candida albicans.
作者信息
Hise Amy G, Tomalka Jeffrey, Ganesan Sandhya, Patel Krupen, Hall Brian A, Brown Gordon D, Fitzgerald Katherine A
机构信息
Center for Global Health and Diseases, Case Western Reserve University, Cleveland, OH 44106, USA.
出版信息
Cell Host Microbe. 2009 May 8;5(5):487-97. doi: 10.1016/j.chom.2009.05.002.
Candida albicans is an opportunistic fungal pathogen causing life-threatening mucosal and systemic infections in immunocompromised humans. Using a murine model of mucosal Candida infection, we investigated the role of the proinflammatory cytokine IL-1beta in host defense to Candida albicans. We find that the synthesis, processing, and release of IL-1beta in response to Candida are tightly controlled and first require transcriptional induction, followed by a second signal leading to caspase-1-mediated cleavage of the pro-IL-1beta cytokine. The known fungal pattern recognition receptors TLR2 and Dectin-1 regulate IL-1beta gene transcription, whereas the NLRP3-containing proinflammatory multiprotein complex, the NLRP3 inflammasome, controls caspase-1-mediated cleavage of pro-IL-1beta. Furthermore, we show that TLR2, Dectin-1, and NLRP3 are essential for defense against dissemination of mucosal infection and mortality in vivo. Therefore, in addition to sensing bacterial and viral pathogens, the NLRP3 inflammasome senses fungal pathogens and is critical in host defense against Candida.
白色念珠菌是一种机会性真菌病原体，可在免疫功能低下的人群中引起危及生命的黏膜和全身感染。我们使用黏膜念珠菌感染的小鼠模型，研究了促炎细胞因子白细胞介素-1β（IL-1β）在宿主抵御白色念珠菌中的作用。我们发现，对念珠菌作出反应时，IL-1β的合成、加工和释放受到严格控制，首先需要转录诱导，随后需要第二个信号，导致半胱天冬酶-1介导的前体IL-1β细胞因子的切割。已知的真菌模式识别受体Toll样受体2（TLR2）和脱铁蛋白1（Dectin-1）调节IL-1β基因转录，而含NLRP3的促炎多蛋白复合物NLRP3炎性小体则控制半胱天冬酶-1介导的前体IL-1β的切割。此外，我们表明TLR2、Dectin-1和NLRP3对于体内抵御黏膜感染的扩散和死亡至关重要。因此，除了感知细菌和病毒病原体外，NLRP3炎性小体还能感知真菌病原体，并且在宿主抵御念珠菌中起关键作用。
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