TMEM16F Expressed in Kupffer Cells Regulates Liver Inflammation and Metabolism to Protect Against Listeria Monocytogenes
Abstract Infection by bacteria leads to tissue damage and inflammation, which need to be tightly controlled by host mechanisms to avoid deleterious consequences. It is previously reported that TMEM16F, a calcium‐activated lipid scramblase expressed in various immune cell types including T cells and...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Wiley
2024-10-01
|
| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202402693 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850206758569508864 |
|---|---|
| author | Jianlong Tang Hua Song Shimin Li Sin Man Lam Jieming Ping Mengyun Yang Na Li Teding Chang Ze Yu Weixiang Liu Yan Lu Min Zhu Zhaohui Tang Zheng Liu Yusong R. Guo Guanghou Shui André Veillette Zhutian Zeng Ning Wu |
| author_facet | Jianlong Tang Hua Song Shimin Li Sin Man Lam Jieming Ping Mengyun Yang Na Li Teding Chang Ze Yu Weixiang Liu Yan Lu Min Zhu Zhaohui Tang Zheng Liu Yusong R. Guo Guanghou Shui André Veillette Zhutian Zeng Ning Wu |
| author_sort | Jianlong Tang |
| collection | DOAJ |
| description | Abstract Infection by bacteria leads to tissue damage and inflammation, which need to be tightly controlled by host mechanisms to avoid deleterious consequences. It is previously reported that TMEM16F, a calcium‐activated lipid scramblase expressed in various immune cell types including T cells and neutrophils, is critical for the control of infection by bacterium Listeria monocytogenes (Lm) in vivo. This function correlated with the capacity of TMEM16F to repair the plasma membrane (PM) damage induced in T cells in vitro, by the Lm toxin listeriolysin O (LLO). However, whether the protective effect of TMEM16F on Lm infection in vivo is mediated by an impact in T cells, or in other cell types, is not determined. Herein, the immune cell types and mechanisms implicated in the protective effect of TMEM16F against Lm in vivo are elucidated. Cellular protective effects of TMEM16F correlated with its capacity of lipid scrambling and augment PM fluidity. Using cell type‐specific TMEM16F‐deficient mice, the indication is obtained that TMEM16F expressed in liver Kupffer cells (KCs), but not in T cells or B cells, is key for protection against Listeria in vivo. In the absence of TMEM16F, Listeria induced PM rupture and fragmentation of KCs in vivo. KC death associated with greater liver damage, inflammatory changes, and dysregulated liver metabolism. Overall, the results uncovered that TMEM16F expressed in Kupffer cells is crucial to protect the host against Listeria infection. This influence is associated with the capacity of Kupffer cell‐expressed TMEM16F to prevent excessive inflammation and abnormal liver metabolism. |
| format | Article |
| id | doaj-art-450c2d021b794d45ad4d02b1ca5d99ce |
| institution | OA Journals |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-450c2d021b794d45ad4d02b1ca5d99ce2025-08-20T02:10:42ZengWileyAdvanced Science2198-38442024-10-011139n/an/a10.1002/advs.202402693TMEM16F Expressed in Kupffer Cells Regulates Liver Inflammation and Metabolism to Protect Against Listeria MonocytogenesJianlong Tang0Hua Song1Shimin Li2Sin Man Lam3Jieming Ping4Mengyun Yang5Na Li6Teding Chang7Ze Yu8Weixiang Liu9Yan Lu10Min Zhu11Zhaohui Tang12Zheng Liu13Yusong R. Guo14Guanghou Shui15André Veillette16Zhutian Zeng17Ning Wu18Department of Immunology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology (HUST) Wuhan 430030 ChinaDepartment of Immunology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology (HUST) Wuhan 430030 ChinaThe CAS Key Laboratory of Innate Immunity and Chronic Disease School of Basic Medical Sciences Division of Life Sciences and Medicine University of Science and Technology of China Hefei 230001 ChinaState Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing 100101 ChinaDepartment of Immunology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology (HUST) Wuhan 430030 ChinaDepartment of Immunology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology (HUST) Wuhan 430030 ChinaDepartment of biochemistry and molecular biology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 ChinaDepartment of Traumatic Surgery Tongji Trauma Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 ChinaDepartment of Otolaryngology‐Head and Neck Surgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology No. 1095 Jiefang Avenue Wuhan 430030 ChinaDepartment of Immunology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology (HUST) Wuhan 430030 ChinaDepartment of Clinical Immunology The Third Affiliated Hospital of Sun Yat‐sen University Guangzhou 510630 ChinaDepartment of Thoracic Surgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 ChinaDepartment of Traumatic Surgery Tongji Trauma Center Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 ChinaDepartment of Otolaryngology‐Head and Neck Surgery Tongji Hospital Tongji Medical College Huazhong University of Science and Technology No. 1095 Jiefang Avenue Wuhan 430030 ChinaDepartment of biochemistry and molecular biology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology Wuhan 430030 ChinaState Key Laboratory of Molecular Developmental Biology Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing 100101 ChinaLaboratory of Molecular Oncology Institut de recherches cliniques de Montréal (IRCM) Montréal Québec H2W1R7 CanadaThe CAS Key Laboratory of Innate Immunity and Chronic Disease School of Basic Medical Sciences Division of Life Sciences and Medicine University of Science and Technology of China Hefei 230001 ChinaDepartment of Immunology School of Basic Medicine Tongji Medical College Huazhong University of Science and Technology (HUST) Wuhan 430030 ChinaAbstract Infection by bacteria leads to tissue damage and inflammation, which need to be tightly controlled by host mechanisms to avoid deleterious consequences. It is previously reported that TMEM16F, a calcium‐activated lipid scramblase expressed in various immune cell types including T cells and neutrophils, is critical for the control of infection by bacterium Listeria monocytogenes (Lm) in vivo. This function correlated with the capacity of TMEM16F to repair the plasma membrane (PM) damage induced in T cells in vitro, by the Lm toxin listeriolysin O (LLO). However, whether the protective effect of TMEM16F on Lm infection in vivo is mediated by an impact in T cells, or in other cell types, is not determined. Herein, the immune cell types and mechanisms implicated in the protective effect of TMEM16F against Lm in vivo are elucidated. Cellular protective effects of TMEM16F correlated with its capacity of lipid scrambling and augment PM fluidity. Using cell type‐specific TMEM16F‐deficient mice, the indication is obtained that TMEM16F expressed in liver Kupffer cells (KCs), but not in T cells or B cells, is key for protection against Listeria in vivo. In the absence of TMEM16F, Listeria induced PM rupture and fragmentation of KCs in vivo. KC death associated with greater liver damage, inflammatory changes, and dysregulated liver metabolism. Overall, the results uncovered that TMEM16F expressed in Kupffer cells is crucial to protect the host against Listeria infection. This influence is associated with the capacity of Kupffer cell‐expressed TMEM16F to prevent excessive inflammation and abnormal liver metabolism.https://doi.org/10.1002/advs.202402693inflammationkupffer celllipid scramblinglisteria monocytogenesmacrophageplasma membrane integrity |
| spellingShingle | Jianlong Tang Hua Song Shimin Li Sin Man Lam Jieming Ping Mengyun Yang Na Li Teding Chang Ze Yu Weixiang Liu Yan Lu Min Zhu Zhaohui Tang Zheng Liu Yusong R. Guo Guanghou Shui André Veillette Zhutian Zeng Ning Wu TMEM16F Expressed in Kupffer Cells Regulates Liver Inflammation and Metabolism to Protect Against Listeria Monocytogenes Advanced Science inflammation kupffer cell lipid scrambling listeria monocytogenes macrophage plasma membrane integrity |
| title | TMEM16F Expressed in Kupffer Cells Regulates Liver Inflammation and Metabolism to Protect Against Listeria Monocytogenes |
| title_full | TMEM16F Expressed in Kupffer Cells Regulates Liver Inflammation and Metabolism to Protect Against Listeria Monocytogenes |
| title_fullStr | TMEM16F Expressed in Kupffer Cells Regulates Liver Inflammation and Metabolism to Protect Against Listeria Monocytogenes |
| title_full_unstemmed | TMEM16F Expressed in Kupffer Cells Regulates Liver Inflammation and Metabolism to Protect Against Listeria Monocytogenes |
| title_short | TMEM16F Expressed in Kupffer Cells Regulates Liver Inflammation and Metabolism to Protect Against Listeria Monocytogenes |
| title_sort | tmem16f expressed in kupffer cells regulates liver inflammation and metabolism to protect against listeria monocytogenes |
| topic | inflammation kupffer cell lipid scrambling listeria monocytogenes macrophage plasma membrane integrity |
| url | https://doi.org/10.1002/advs.202402693 |
| work_keys_str_mv | AT jianlongtang tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes AT huasong tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes AT shiminli tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes AT sinmanlam tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes AT jiemingping tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes AT mengyunyang tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes AT nali tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes AT tedingchang tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes AT zeyu tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes AT weixiangliu tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes AT yanlu tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes AT minzhu tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes AT zhaohuitang tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes AT zhengliu tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes AT yusongrguo tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes AT guanghoushui tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes AT andreveillette tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes AT zhutianzeng tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes AT ningwu tmem16fexpressedinkupffercellsregulatesliverinflammationandmetabolismtoprotectagainstlisteriamonocytogenes |