Mycobacterium tuberculosis hijacks host macrophages-derived interleukin 16 to block phagolysosome maturation for enhancing intracellular growth
The discovery of promising cytokines and clarification of their immunological mechanisms in controlling the intracellular fate of Mycobacterium tuberculosis (Mtb) are necessary to identify effective diagnostic biomarkers and therapeutic targets. To escape immune clearance, Mtb can manipulate and inh...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Emerging Microbes and Infections |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/22221751.2024.2322663 |
| _version_ | 1826947177075703808 |
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| author | Haibo Su Shufeng Weng Liulin Luo Qin Sun Taiyue Lin Huixia Ma Yumo He Jing Wu Honghai Wang Wenhong Zhang Ying Xu |
| author_facet | Haibo Su Shufeng Weng Liulin Luo Qin Sun Taiyue Lin Huixia Ma Yumo He Jing Wu Honghai Wang Wenhong Zhang Ying Xu |
| author_sort | Haibo Su |
| collection | DOAJ |
| description | The discovery of promising cytokines and clarification of their immunological mechanisms in controlling the intracellular fate of Mycobacterium tuberculosis (Mtb) are necessary to identify effective diagnostic biomarkers and therapeutic targets. To escape immune clearance, Mtb can manipulate and inhibit the normal host process of phagosome maturation. Phagosome maturation arrest by Mtb involves multiple effectors and much remains unknown about this important aspect of Mtb pathogenesis. In this study, we found that interleukin 16 (IL-16) is elevated in the serum samples of Tuberculosis (TB) patients and can serve as a specific target for treatment TB. There was a significant difference in IL-16 levels among active TB, latent TB infection (LTBI), and non-TB patients. This study first revealed that macrophages are the major source of IL-16 production in response to Mtb infection, and elucidated that IL-16 can promote Mtb intracellular survival by inhibiting phagosome maturation and suppressing the expression of Rev-erbα which can inhibit IL-10 secretion. The experiments using zebrafish larvae infected with M. marinum and mice challenged with H37Rv demonstrated that reducing IL-16 levels resulted in less severe pathology and improved survival, respectively. In conclusion, this study provided direct evidence that Mtb hijacks the host macrophages-derived interleukin 16 to enhance intracellular growth. It is suggesting the immunosuppressive role of IL-16 during Mtb infection, supporting IL-16 as a promising therapeutic target. |
| first_indexed | 2024-03-07T16:23:32Z |
| format | Article |
| id | doaj.art-49cabce2b4c54256b5ec7940d0a36fea |
| institution | Directory Open Access Journal |
| issn | 2222-1751 |
| language | English |
| last_indexed | 2025-02-17T21:26:28Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Emerging Microbes and Infections |
| spelling | doaj.art-49cabce2b4c54256b5ec7940d0a36fea2024-12-07T04:40:18ZengTaylor & Francis GroupEmerging Microbes and Infections2222-17512024-12-0113110.1080/22221751.2024.2322663Mycobacterium tuberculosis hijacks host macrophages-derived interleukin 16 to block phagolysosome maturation for enhancing intracellular growthHaibo Su0Shufeng Weng1Liulin Luo2Qin Sun3Taiyue Lin4Huixia Ma5Yumo He6Jing Wu7Honghai Wang8Wenhong Zhang9Ying Xu10State Key Laboratory of Genetic Engineering, School of Life Sciences, Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaState Key Laboratory of Genetic Engineering, School of Life Sciences, Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaDepartment of Clinical Laboratory, Yangpu Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of ChinaShanghai Clinical Research Center for Infectious Disease (Tuberculosis), Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of ChinaState Key Laboratory of Genetic Engineering, School of Life Sciences, Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaState Key Laboratory of Genetic Engineering, School of Life Sciences, Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaState Key Laboratory of Genetic Engineering, School of Life Sciences, Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaState Key Laboratory of Genetic Engineering, School of Life Sciences, Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaState Key Laboratory of Genetic Engineering, School of Life Sciences, Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaState Key Laboratory of Genetic Engineering, School of Life Sciences, Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaState Key Laboratory of Genetic Engineering, School of Life Sciences, Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, People’s Republic of ChinaThe discovery of promising cytokines and clarification of their immunological mechanisms in controlling the intracellular fate of Mycobacterium tuberculosis (Mtb) are necessary to identify effective diagnostic biomarkers and therapeutic targets. To escape immune clearance, Mtb can manipulate and inhibit the normal host process of phagosome maturation. Phagosome maturation arrest by Mtb involves multiple effectors and much remains unknown about this important aspect of Mtb pathogenesis. In this study, we found that interleukin 16 (IL-16) is elevated in the serum samples of Tuberculosis (TB) patients and can serve as a specific target for treatment TB. There was a significant difference in IL-16 levels among active TB, latent TB infection (LTBI), and non-TB patients. This study first revealed that macrophages are the major source of IL-16 production in response to Mtb infection, and elucidated that IL-16 can promote Mtb intracellular survival by inhibiting phagosome maturation and suppressing the expression of Rev-erbα which can inhibit IL-10 secretion. The experiments using zebrafish larvae infected with M. marinum and mice challenged with H37Rv demonstrated that reducing IL-16 levels resulted in less severe pathology and improved survival, respectively. In conclusion, this study provided direct evidence that Mtb hijacks the host macrophages-derived interleukin 16 to enhance intracellular growth. It is suggesting the immunosuppressive role of IL-16 during Mtb infection, supporting IL-16 as a promising therapeutic target.https://www.tandfonline.com/doi/10.1080/22221751.2024.2322663Mycobacterium tuberculosisphagolysosome conversionIL-16macrophagesTB |
| spellingShingle | Haibo Su Shufeng Weng Liulin Luo Qin Sun Taiyue Lin Huixia Ma Yumo He Jing Wu Honghai Wang Wenhong Zhang Ying Xu Mycobacterium tuberculosis hijacks host macrophages-derived interleukin 16 to block phagolysosome maturation for enhancing intracellular growth Emerging Microbes and Infections Mycobacterium tuberculosis phagolysosome conversion IL-16 macrophages TB |
| title | Mycobacterium tuberculosis hijacks host macrophages-derived interleukin 16 to block phagolysosome maturation for enhancing intracellular growth |
| title_full | Mycobacterium tuberculosis hijacks host macrophages-derived interleukin 16 to block phagolysosome maturation for enhancing intracellular growth |
| title_fullStr | Mycobacterium tuberculosis hijacks host macrophages-derived interleukin 16 to block phagolysosome maturation for enhancing intracellular growth |
| title_full_unstemmed | Mycobacterium tuberculosis hijacks host macrophages-derived interleukin 16 to block phagolysosome maturation for enhancing intracellular growth |
| title_short | Mycobacterium tuberculosis hijacks host macrophages-derived interleukin 16 to block phagolysosome maturation for enhancing intracellular growth |
| title_sort | mycobacterium tuberculosis hijacks host macrophages derived interleukin 16 to block phagolysosome maturation for enhancing intracellular growth |
| topic | Mycobacterium tuberculosis phagolysosome conversion IL-16 macrophages TB |
| url | https://www.tandfonline.com/doi/10.1080/22221751.2024.2322663 |
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