Piezo1 senses hyphae and initiates host defense against pathogenic fungi
Summary: 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 indispensab...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124725006102 |
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| author | Yiran Shi Bingying Yang Yueyue Linghu Yue Liu Haoran Li Yunzhi Xing Binbin Wu Yuting Gao Liuqi Liao Yi Zheng Lei Pan Xiufeng Sun Qinghua Chen Yongqiang Hou Dongxue Su Hongling Huang Jiahuai Han Shih-Chin Cheng Dawang Zhou Lanfen Chen |
| author_facet | Yiran Shi Bingying Yang Yueyue Linghu Yue Liu Haoran Li Yunzhi Xing Binbin Wu Yuting Gao Liuqi Liao Yi Zheng Lei Pan Xiufeng Sun Qinghua Chen Yongqiang Hou Dongxue Su Hongling Huang Jiahuai Han Shih-Chin Cheng Dawang Zhou Lanfen Chen |
| author_sort | Yiran Shi |
| collection | DOAJ |
| description | Summary: 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/Ca2+/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. |
| format | Article |
| id | doaj-art-3230a31c858f4ff4aa91e9cfb8ebe3d2 |
| institution | OA Journals |
| issn | 2211-1247 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj-art-3230a31c858f4ff4aa91e9cfb8ebe3d22025-08-20T02:07:35ZengElsevierCell Reports2211-12472025-06-0144611583910.1016/j.celrep.2025.115839Piezo1 senses hyphae and initiates host defense against pathogenic fungiYiran Shi0Bingying Yang1Yueyue Linghu2Yue Liu3Haoran Li4Yunzhi Xing5Binbin Wu6Yuting Gao7Liuqi Liao8Yi Zheng9Lei Pan10Xiufeng Sun11Qinghua Chen12Yongqiang Hou13Dongxue Su14Hongling Huang15Jiahuai Han16Shih-Chin Cheng17Dawang Zhou18Lanfen Chen19State Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState 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, ChinaState Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState Key Laboratory of Cellular Stress Biology, Xiang'an Hospital, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, Fujian 361102, ChinaState 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; Xiang An Biomedicine Laboratory, Xiamen University, Xiamen, Fujian 361102, China; Corresponding authorSummary: 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/Ca2+/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.http://www.sciencedirect.com/science/article/pii/S2211124725006102CP: ImmunologyCP: Microbiology |
| spellingShingle | Yiran Shi Bingying Yang Yueyue Linghu Yue Liu Haoran Li Yunzhi Xing Binbin Wu Yuting Gao Liuqi Liao Yi Zheng Lei Pan Xiufeng Sun Qinghua Chen Yongqiang Hou Dongxue Su Hongling Huang Jiahuai Han Shih-Chin Cheng Dawang Zhou Lanfen Chen Piezo1 senses hyphae and initiates host defense against pathogenic fungi Cell Reports CP: Immunology CP: Microbiology |
| title | Piezo1 senses hyphae and initiates host defense against pathogenic fungi |
| title_full | Piezo1 senses hyphae and initiates host defense against pathogenic fungi |
| title_fullStr | Piezo1 senses hyphae and initiates host defense against pathogenic fungi |
| title_full_unstemmed | Piezo1 senses hyphae and initiates host defense against pathogenic fungi |
| title_short | Piezo1 senses hyphae and initiates host defense against pathogenic fungi |
| title_sort | piezo1 senses hyphae and initiates host defense against pathogenic fungi |
| topic | CP: Immunology CP: Microbiology |
| url | http://www.sciencedirect.com/science/article/pii/S2211124725006102 |
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