Shi Yiran, Yang Bingying, Linghu Yueyue, Liu Yue, Li Haoran, Xing Yunzhi, Wu Binbin, Gao Yuting, Liao Liuqi, Zheng Yi, Pan Lei, Sun Xiufeng, Chen Qinghua, Hou Yongqiang, Su Dongxue, Huang Hongling, Han Jiahuai, Cheng Shih-Chin, Zhou Dawang, Chen Lanfen
State Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
State Key Laboratory of Cellular Stress Biology, Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, Institute of Neuroscience, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, China.
Cell Rep. 2025 Jun 24;44(6):115839. doi: 10.1016/j.celrep.2025.115839. Epub 2025 Jun 16.
Candida albicans metamorphoses from benign yeast to a rigid hyphal, becoming an opportunistic pathogen in immunocompromised patients. The process by which immune cells discern fungal transformations remains elusive. Here, we report that the mechanosensitive ion channel Piezo1 is indispensable for recognizing fungal hyphae and triggering antifungal innate immune responses. Hyphae-triggered Piezo1 activation increased C-type lectin receptor (CLR) expression in innate immune cells by inducing the expression of CCAAT/enhancer-binding protein beta (C/EBPβ) via the Piezo1/Ca/calmodulin-dependent kinase (CaMK)/cAMP response element-binding protein (CREB) axis. In addition, Piezo1/CaMK signaling activated kinases nuclear Dbf2-related protein 1/2 (NDR1/2), which augmented NLRP3 inflammasome assembly and promoted hyphae-induced inflammation. Abolishing the yeast-to-hyphae transition dampens CLR expression and NLRP3 activation. Piezo1-deficient mice exhibit compromised clearance of C. albicans infection, whereas Piezo1 agonist amplifies C. albicans clearance. In addition, CaMK, CREB, or NDR1/2 inhibition exacerbates hyphae infections, such as Piezo1 deficiency. Therefore, we ascertain Piezo1-mediated mechanotransduction as vital for immune surveillance and control of hyphal C. albicans, heralding Piezo1 agonist as a potential remedy for fungal infections.
白色念珠菌可从良性酵母形态转变为坚硬的菌丝形态，成为免疫功能低下患者的机会性病原体。免疫细胞识别真菌形态转变的过程仍不清楚。在此，我们报告机械敏感离子通道Piezo1对于识别真菌菌丝和触发抗真菌固有免疫反应必不可少。菌丝触发的Piezo1激活通过Piezo1/钙/钙调蛋白依赖性激酶（CaMK）/环磷酸腺苷反应元件结合蛋白（CREB）轴诱导CCAAT/增强子结合蛋白β（C/EBPβ）的表达，从而增加固有免疫细胞中C型凝集素受体（CLR）的表达。此外，Piezo1/CaMK信号激活激酶核Dbf2相关蛋白1/2（NDR1/2），增强NLRP3炎性小体组装并促进菌丝诱导的炎症。消除酵母到菌丝的转变会抑制CLR表达和NLRP3激活。缺乏Piezo1的小鼠对白色念珠菌感染的清除能力受损，而Piezo1激动剂可增强白色念珠菌的清除。此外，CaMK、CREB或NDR1/2抑制会加剧菌丝感染，如Piezo1缺乏症。因此，我们确定Piezo1介导的机械转导对于白色念珠菌菌丝的免疫监测和控制至关重要，预示着Piezo1激动剂可能是真菌感染的一种潜在治疗方法。
