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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Taylor & Francis Group
2025-12-01
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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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institution | Kabale University |
issn | 1949-0976 1949-0984 |
language | English |
publishDate | 2025-12-01 |
publisher | Taylor & Francis Group |
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series | Gut Microbes |
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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