Gingipain regulates isoform switches of PD-L1 in macrophages infected with Porphyromonas gingivalis
Abstract Periodontal pathogen Porphyromonas gingivalis (P. gingivalis) is believed to possess immune evasion capabilities, but it remains unclear whether this immune evasion is related to host gene alternative splicing (AS). In this study, RNA-sequencing revealed significant changes in both AS lands...
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Nature Portfolio
2025-03-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-94954-7 |
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| author | Yilin Zheng Ziyi Wang Yao Weng Heriati Sitosari Yuhan He Xiu Zhang Noriko Shiotsu Yoko Fukuhara Mika Ikegame Hirohiko Okamura |
| author_facet | Yilin Zheng Ziyi Wang Yao Weng Heriati Sitosari Yuhan He Xiu Zhang Noriko Shiotsu Yoko Fukuhara Mika Ikegame Hirohiko Okamura |
| author_sort | Yilin Zheng |
| collection | DOAJ |
| description | Abstract Periodontal pathogen Porphyromonas gingivalis (P. gingivalis) is believed to possess immune evasion capabilities, but it remains unclear whether this immune evasion is related to host gene alternative splicing (AS). In this study, RNA-sequencing revealed significant changes in both AS landscape and transcriptomic profile of macrophages following P. gingivalis infection with/without knockout of gingipain (a unique toxic protease of P. gingivalis). P. gingivalis infection increased the PD-L1 transcripts expression and selectively upregulated a specific coding isoform that more effectively binds to PD-1 on T cells, thereby inhibiting immune function. Biological experiments also detected AS switch of PD-L1 in P. gingivalis-infected or gingipain-treated macrophages. AlphaFold 3 predictions indicated that the protein docking compatibility between PD-1 and P. gingivalis-upregulated PD-L1 isoform was over 80% higher than another coding isoform. These findings suggest that P. gingivalis employs gingipain to modulate the AS of PD-L1, facilitating immune evasion. |
| format | Article |
| id | doaj-art-8b4eec7b51da4c06a6e79788505166bd |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-8b4eec7b51da4c06a6e79788505166bd2025-08-20T03:40:48ZengNature PortfolioScientific Reports2045-23222025-03-0115111510.1038/s41598-025-94954-7Gingipain regulates isoform switches of PD-L1 in macrophages infected with Porphyromonas gingivalisYilin Zheng0Ziyi Wang1Yao Weng2Heriati Sitosari3Yuhan He4Xiu Zhang5Noriko Shiotsu6Yoko Fukuhara7Mika Ikegame8Hirohiko Okamura9Department of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama UniversityDepartment of Molecular Biology and Biochemistry, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama UniversityDepartment of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama UniversityDepartment of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama UniversityDepartment of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama UniversityDepartment of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama UniversityComprehensive Dental Clinic, Okayama University Hospital, Okayama UniversityDepartment of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama UniversityDepartment of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama UniversityDepartment of Oral Morphology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University Hospital, Okayama UniversityAbstract Periodontal pathogen Porphyromonas gingivalis (P. gingivalis) is believed to possess immune evasion capabilities, but it remains unclear whether this immune evasion is related to host gene alternative splicing (AS). In this study, RNA-sequencing revealed significant changes in both AS landscape and transcriptomic profile of macrophages following P. gingivalis infection with/without knockout of gingipain (a unique toxic protease of P. gingivalis). P. gingivalis infection increased the PD-L1 transcripts expression and selectively upregulated a specific coding isoform that more effectively binds to PD-1 on T cells, thereby inhibiting immune function. Biological experiments also detected AS switch of PD-L1 in P. gingivalis-infected or gingipain-treated macrophages. AlphaFold 3 predictions indicated that the protein docking compatibility between PD-1 and P. gingivalis-upregulated PD-L1 isoform was over 80% higher than another coding isoform. These findings suggest that P. gingivalis employs gingipain to modulate the AS of PD-L1, facilitating immune evasion.https://doi.org/10.1038/s41598-025-94954-7Porphyromonas gingivalisGingipainMacrophageAlternative splicingPD-L1Immune evasion |
| spellingShingle | Yilin Zheng Ziyi Wang Yao Weng Heriati Sitosari Yuhan He Xiu Zhang Noriko Shiotsu Yoko Fukuhara Mika Ikegame Hirohiko Okamura Gingipain regulates isoform switches of PD-L1 in macrophages infected with Porphyromonas gingivalis Scientific Reports Porphyromonas gingivalis Gingipain Macrophage Alternative splicing PD-L1 Immune evasion |
| title | Gingipain regulates isoform switches of PD-L1 in macrophages infected with Porphyromonas gingivalis |
| title_full | Gingipain regulates isoform switches of PD-L1 in macrophages infected with Porphyromonas gingivalis |
| title_fullStr | Gingipain regulates isoform switches of PD-L1 in macrophages infected with Porphyromonas gingivalis |
| title_full_unstemmed | Gingipain regulates isoform switches of PD-L1 in macrophages infected with Porphyromonas gingivalis |
| title_short | Gingipain regulates isoform switches of PD-L1 in macrophages infected with Porphyromonas gingivalis |
| title_sort | gingipain regulates isoform switches of pd l1 in macrophages infected with porphyromonas gingivalis |
| topic | Porphyromonas gingivalis Gingipain Macrophage Alternative splicing PD-L1 Immune evasion |
| url | https://doi.org/10.1038/s41598-025-94954-7 |
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