Candida albicans aspartyl protease (Sap6) inhibits neutrophil function via a “Trojan horse” mechanism
Abstract Candida albicans, a prevalent fungal pathogen, employs aspartyl proteases such as Sap6 to evade immune defenses, challenging our understanding of host‒pathogen interactions. This research examined the impact of Sap6 on neutrophil responses, which are crucial for innate immunity. Employing f...
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Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-91425-x |
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| author | Marcin Zawrotniak Dorota Satala Magdalena Juszczak Grażyna Bras Maria Rapala-Kozik |
| author_facet | Marcin Zawrotniak Dorota Satala Magdalena Juszczak Grażyna Bras Maria Rapala-Kozik |
| author_sort | Marcin Zawrotniak |
| collection | DOAJ |
| description | Abstract Candida albicans, a prevalent fungal pathogen, employs aspartyl proteases such as Sap6 to evade immune defenses, challenging our understanding of host‒pathogen interactions. This research examined the impact of Sap6 on neutrophil responses, which are crucial for innate immunity. Employing flow cytometry and fluorescence microscopy, we explored how Sap6 affects neutrophil functions, particularly by focusing on reactive oxygen species (ROS) production, neutrophil extracellular traps release (NETosis), and apoptosis. Our findings revealed Sap6’s unique ability to bind and internalize in neutrophils, significantly attenuating ROS production through proteolytic damage to NADPH oxidase, resulting in blocking the ROS-dependent NETosis pathway. This disruption in neutrophil functions by Sap6 suggested the presence of a ‘Trojan horse’ mechanism by C. albicans. This mechanism reveals a sophisticated immune evasion strategy, shedding light on fungal pathogenicity and host immune interactions. Understanding fungal proteases in immune modulation could inspire new therapeutic approaches for fungal infections. |
| format | Article |
| id | doaj-art-972f01b24b8a49ac8e015fd7597bf00c |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-972f01b24b8a49ac8e015fd7597bf00c2025-08-20T02:16:45ZengNature PortfolioScientific Reports2045-23222025-02-0115111910.1038/s41598-025-91425-xCandida albicans aspartyl protease (Sap6) inhibits neutrophil function via a “Trojan horse” mechanismMarcin Zawrotniak0Dorota Satala1Magdalena Juszczak2Grażyna Bras3Maria Rapala-Kozik4Department of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityDepartment of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityDepartment of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityDepartment of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityDepartment of Comparative Biochemistry and Bioanalytics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian UniversityAbstract Candida albicans, a prevalent fungal pathogen, employs aspartyl proteases such as Sap6 to evade immune defenses, challenging our understanding of host‒pathogen interactions. This research examined the impact of Sap6 on neutrophil responses, which are crucial for innate immunity. Employing flow cytometry and fluorescence microscopy, we explored how Sap6 affects neutrophil functions, particularly by focusing on reactive oxygen species (ROS) production, neutrophil extracellular traps release (NETosis), and apoptosis. Our findings revealed Sap6’s unique ability to bind and internalize in neutrophils, significantly attenuating ROS production through proteolytic damage to NADPH oxidase, resulting in blocking the ROS-dependent NETosis pathway. This disruption in neutrophil functions by Sap6 suggested the presence of a ‘Trojan horse’ mechanism by C. albicans. This mechanism reveals a sophisticated immune evasion strategy, shedding light on fungal pathogenicity and host immune interactions. Understanding fungal proteases in immune modulation could inspire new therapeutic approaches for fungal infections.https://doi.org/10.1038/s41598-025-91425-xCandida albicansNeutrophilsAspartic proteasesApoptosisNeutrophil extracellular trapsReactive oxygen species |
| spellingShingle | Marcin Zawrotniak Dorota Satala Magdalena Juszczak Grażyna Bras Maria Rapala-Kozik Candida albicans aspartyl protease (Sap6) inhibits neutrophil function via a “Trojan horse” mechanism Scientific Reports Candida albicans Neutrophils Aspartic proteases Apoptosis Neutrophil extracellular traps Reactive oxygen species |
| title | Candida albicans aspartyl protease (Sap6) inhibits neutrophil function via a “Trojan horse” mechanism |
| title_full | Candida albicans aspartyl protease (Sap6) inhibits neutrophil function via a “Trojan horse” mechanism |
| title_fullStr | Candida albicans aspartyl protease (Sap6) inhibits neutrophil function via a “Trojan horse” mechanism |
| title_full_unstemmed | Candida albicans aspartyl protease (Sap6) inhibits neutrophil function via a “Trojan horse” mechanism |
| title_short | Candida albicans aspartyl protease (Sap6) inhibits neutrophil function via a “Trojan horse” mechanism |
| title_sort | candida albicans aspartyl protease sap6 inhibits neutrophil function via a trojan horse mechanism |
| topic | Candida albicans Neutrophils Aspartic proteases Apoptosis Neutrophil extracellular traps Reactive oxygen species |
| url | https://doi.org/10.1038/s41598-025-91425-x |
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