PMA1-containing extracellular vesicles of Candida albicans triggers immune responses and colitis progression

Candida albicans (C. albicans) exhibits aberrant changes in patients with colitis, and it has been reported to dominate the colonic mucosal immune response. Here, we found that PMA1 expression was significantly increased in C. albicans from patients with IBD compared to that in healthy controls. A C...

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Main Authors: Zhen Xu, Shuping Qiao, Zelin Wang, Chen Peng, Yayi Hou, Baorui Liu, Guochun Cao, Tingting Wang
Format: Article
Language:English
Published: Taylor & Francis Group 2025-12-01
Series:Gut Microbes
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Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2025.2455508
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author Zhen Xu
Shuping Qiao
Zelin Wang
Chen Peng
Yayi Hou
Baorui Liu
Guochun Cao
Tingting Wang
author_facet Zhen Xu
Shuping Qiao
Zelin Wang
Chen Peng
Yayi Hou
Baorui Liu
Guochun Cao
Tingting Wang
author_sort Zhen Xu
collection DOAJ
description Candida albicans (C. albicans) exhibits aberrant changes in patients with colitis, and it has been reported to dominate the colonic mucosal immune response. Here, we found that PMA1 expression was significantly increased in C. albicans from patients with IBD compared to that in healthy controls. A Crispr-Cas9-based fungal strain editing system was then used to knock out PMA1 expression in C. albicans. Compared to WT-C.a, ΔPMA1-C.a could not aggravate colitis. Proteomic analysis showed that PMA1 was transported by extracellular vesicles (EVs) of C. albicans. PMA1-containing EVs aggravated colitis, modulated the migration of cDC2 from the lamina propria to mesenteric lymph nodes, and induced TH17 cell differentiation. Moreover, the adaptor protein CARD9 was critical in PMA1-containing EV-induced colitis, and CARD9-deficient DCs did not induce TH17 cell differentiation or IL-17A production. Mechanically, CARD9 combines with the glycolytic protein GAPDH (aa2–146 domain) through its CARD region. CARD9 deficiency led to decreased enzyme activity of GAPDH and decreased glycolysis of DCs. These findings indicate that PMA1 is a potential virulence factor responsible for the pathogenesis of C. albicans colitis.
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spelling doaj-art-408ddc53a99740ad9ee0a87f81df7fe92025-01-31T10:06:12ZengTaylor & Francis GroupGut Microbes1949-09761949-09842025-12-0117110.1080/19490976.2025.2455508PMA1-containing extracellular vesicles of Candida albicans triggers immune responses and colitis progressionZhen Xu0Shuping Qiao1Zelin Wang2Chen Peng3Yayi Hou4Baorui Liu5Guochun Cao6Tingting Wang7Department of Oncology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDepartment of Oncology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDepartment of Oncology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDepartment of Oncology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDepartment of Oncology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDepartment of Oncology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaDepartment of Medical Oncology, Jiangsu Cancer Hospital & Jiangsu Institute of Cancer Research & The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, ChinaDepartment of Oncology, Nanjing Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Affiliated Hospital of Medical School, Nanjing University, Nanjing, ChinaCandida albicans (C. albicans) exhibits aberrant changes in patients with colitis, and it has been reported to dominate the colonic mucosal immune response. Here, we found that PMA1 expression was significantly increased in C. albicans from patients with IBD compared to that in healthy controls. A Crispr-Cas9-based fungal strain editing system was then used to knock out PMA1 expression in C. albicans. Compared to WT-C.a, ΔPMA1-C.a could not aggravate colitis. Proteomic analysis showed that PMA1 was transported by extracellular vesicles (EVs) of C. albicans. PMA1-containing EVs aggravated colitis, modulated the migration of cDC2 from the lamina propria to mesenteric lymph nodes, and induced TH17 cell differentiation. Moreover, the adaptor protein CARD9 was critical in PMA1-containing EV-induced colitis, and CARD9-deficient DCs did not induce TH17 cell differentiation or IL-17A production. Mechanically, CARD9 combines with the glycolytic protein GAPDH (aa2–146 domain) through its CARD region. CARD9 deficiency led to decreased enzyme activity of GAPDH and decreased glycolysis of DCs. These findings indicate that PMA1 is a potential virulence factor responsible for the pathogenesis of C. albicans colitis.https://www.tandfonline.com/doi/10.1080/19490976.2025.2455508C. albicansextracellular vesiclesPMA1dendritic cellcolitis
spellingShingle Zhen Xu
Shuping Qiao
Zelin Wang
Chen Peng
Yayi Hou
Baorui Liu
Guochun Cao
Tingting Wang
PMA1-containing extracellular vesicles of Candida albicans triggers immune responses and colitis progression
Gut Microbes
C. albicans
extracellular vesicles
PMA1
dendritic cell
colitis
title PMA1-containing extracellular vesicles of Candida albicans triggers immune responses and colitis progression
title_full PMA1-containing extracellular vesicles of Candida albicans triggers immune responses and colitis progression
title_fullStr PMA1-containing extracellular vesicles of Candida albicans triggers immune responses and colitis progression
title_full_unstemmed PMA1-containing extracellular vesicles of Candida albicans triggers immune responses and colitis progression
title_short PMA1-containing extracellular vesicles of Candida albicans triggers immune responses and colitis progression
title_sort pma1 containing extracellular vesicles of candida albicans triggers immune responses and colitis progression
topic C. albicans
extracellular vesicles
PMA1
dendritic cell
colitis
url https://www.tandfonline.com/doi/10.1080/19490976.2025.2455508
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