Hantaan virus infection induces human mucosal-associated invariant T cell pyroptosis through IRE1α pathway
Abstract Hantaan virus (HTNV) triggers an epidemic of hemorrhagic fever with renal syndrome (HFRS), which is predominantly prevalent in Asia. Mucosal-associated invariant T (MAIT) cells, categorized as innate-like T lymphocytes, perform crucial functions in the innate host defense mechanism during v...
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Nature Portfolio
2025-04-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07979-z |
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| author | Yusi Zhang He Liu Dalu Liu Huiyuan Zhang Ying Ma Na Li Chunmei Zhang Manling Xue Fenglan Wang Xiaozhou Jia Hui Zhang Kang Tang Xiaoyue Xu Shijia Wang Yiwen Wei Xiaojing Yang Jiajia Zuo Lihua Chen Boquan Jin Yun Zhang |
| author_facet | Yusi Zhang He Liu Dalu Liu Huiyuan Zhang Ying Ma Na Li Chunmei Zhang Manling Xue Fenglan Wang Xiaozhou Jia Hui Zhang Kang Tang Xiaoyue Xu Shijia Wang Yiwen Wei Xiaojing Yang Jiajia Zuo Lihua Chen Boquan Jin Yun Zhang |
| author_sort | Yusi Zhang |
| collection | DOAJ |
| description | Abstract Hantaan virus (HTNV) triggers an epidemic of hemorrhagic fever with renal syndrome (HFRS), which is predominantly prevalent in Asia. Mucosal-associated invariant T (MAIT) cells, categorized as innate-like T lymphocytes, perform crucial functions in the innate host defense mechanism during virus infection. We previously showed that MAIT cells played antiviral roles in vitro. But marked reduction of MAIT cells was present in the peripheral blood of HFRS patients. Till now, the role of MAIT cells in vivo and the mechanisms of HTNV-induced the MAIT cell deficiency have not yet been fully explored. In this study, by combining the clinical samples, MAIT deficiency mice and in vitro infected MAIT cell models, we find that pyroptosis was the main reason of MAIT cell loss in the peripheral blood of HFRS patients. The molecular mechanisms are related to the overload of calcium in the endoplasmic reticulum (ER) of MAIT cells, which subsequently induces inosital-requiring enzyme-1α (IRE1α)-mediated ER-stress and following pyroptosis. ER-stress inhibitor can reverse the pyroptosis of MAIT cells during HTNV infection. In conclusion, this study firstly reveals the underlying molecular mechanisms for the deficiency of MAIT cells during HTNV infection, and suggests a potential way to stabilize the MAIT cells population in HFRS. |
| format | Article |
| id | doaj-art-93f3ad6805fe427a9be7ed7d7e881e8a |
| institution | OA Journals |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-04-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-93f3ad6805fe427a9be7ed7d7e881e8a2025-08-20T02:25:41ZengNature PortfolioCommunications Biology2399-36422025-04-018111310.1038/s42003-025-07979-zHantaan virus infection induces human mucosal-associated invariant T cell pyroptosis through IRE1α pathwayYusi Zhang0He Liu1Dalu Liu2Huiyuan Zhang3Ying Ma4Na Li5Chunmei Zhang6Manling Xue7Fenglan Wang8Xiaozhou Jia9Hui Zhang10Kang Tang11Xiaoyue Xu12Shijia Wang13Yiwen Wei14Xiaojing Yang15Jiajia Zuo16Lihua Chen17Boquan Jin18Yun Zhang19Department of Immunology, School of Basic Medicine, Fourth Military Medical UniversityDepartment of Microbiology, School of Basic Medicine, Fourth Military Medical UniversityDepartment of Radiation Medicine and Protection, Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, School of Public Health, Fourth Military Medical UniversityDepartment of Immunology, School of Basic Medicine, Fourth Military Medical UniversityDepartment of Immunology, School of Basic Medicine, Fourth Military Medical UniversityDepartment of Transfusion Medicine, Xijing Hospital, Fourth Military Medical UniversityDepartment of Immunology, School of Basic Medicine, Fourth Military Medical UniversityDepartment of Immunology, School of Basic Medicine, Fourth Military Medical UniversityEighth Hospital of Xi’anEighth Hospital of Xi’anDepartment of Microbiology, School of Basic Medicine, Fourth Military Medical UniversityDepartment of Immunology, School of Basic Medicine, Fourth Military Medical UniversityDepartment of Immunology, School of Basic Medicine, Fourth Military Medical UniversityDepartment of Immunology, School of Basic Medicine, Fourth Military Medical UniversityDepartment of Immunology, School of Basic Medicine, Fourth Military Medical UniversityDepartment of Microbiology, School of Basic Medicine, Fourth Military Medical UniversityDepartment of Immunology, School of Basic Medicine, Fourth Military Medical UniversityDepartment of Immunology, School of Basic Medicine, Fourth Military Medical UniversityDepartment of Immunology, School of Basic Medicine, Fourth Military Medical UniversityDepartment of Immunology, School of Basic Medicine, Fourth Military Medical UniversityAbstract Hantaan virus (HTNV) triggers an epidemic of hemorrhagic fever with renal syndrome (HFRS), which is predominantly prevalent in Asia. Mucosal-associated invariant T (MAIT) cells, categorized as innate-like T lymphocytes, perform crucial functions in the innate host defense mechanism during virus infection. We previously showed that MAIT cells played antiviral roles in vitro. But marked reduction of MAIT cells was present in the peripheral blood of HFRS patients. Till now, the role of MAIT cells in vivo and the mechanisms of HTNV-induced the MAIT cell deficiency have not yet been fully explored. In this study, by combining the clinical samples, MAIT deficiency mice and in vitro infected MAIT cell models, we find that pyroptosis was the main reason of MAIT cell loss in the peripheral blood of HFRS patients. The molecular mechanisms are related to the overload of calcium in the endoplasmic reticulum (ER) of MAIT cells, which subsequently induces inosital-requiring enzyme-1α (IRE1α)-mediated ER-stress and following pyroptosis. ER-stress inhibitor can reverse the pyroptosis of MAIT cells during HTNV infection. In conclusion, this study firstly reveals the underlying molecular mechanisms for the deficiency of MAIT cells during HTNV infection, and suggests a potential way to stabilize the MAIT cells population in HFRS.https://doi.org/10.1038/s42003-025-07979-z |
| spellingShingle | Yusi Zhang He Liu Dalu Liu Huiyuan Zhang Ying Ma Na Li Chunmei Zhang Manling Xue Fenglan Wang Xiaozhou Jia Hui Zhang Kang Tang Xiaoyue Xu Shijia Wang Yiwen Wei Xiaojing Yang Jiajia Zuo Lihua Chen Boquan Jin Yun Zhang Hantaan virus infection induces human mucosal-associated invariant T cell pyroptosis through IRE1α pathway Communications Biology |
| title | Hantaan virus infection induces human mucosal-associated invariant T cell pyroptosis through IRE1α pathway |
| title_full | Hantaan virus infection induces human mucosal-associated invariant T cell pyroptosis through IRE1α pathway |
| title_fullStr | Hantaan virus infection induces human mucosal-associated invariant T cell pyroptosis through IRE1α pathway |
| title_full_unstemmed | Hantaan virus infection induces human mucosal-associated invariant T cell pyroptosis through IRE1α pathway |
| title_short | Hantaan virus infection induces human mucosal-associated invariant T cell pyroptosis through IRE1α pathway |
| title_sort | hantaan virus infection induces human mucosal associated invariant t cell pyroptosis through ire1α pathway |
| url | https://doi.org/10.1038/s42003-025-07979-z |
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