mTORC2 is crucial for regulating the recombinant Mycobacterium tuberculosis CFP-10 protein-induced phagocytosis in macrophages
Abstract Mycobacterium tuberculosis (M. tuberculosis, Mtb) is a pathogenic bacterial species in the family Mycobacteriaceae and the causative agent of most cases of tuberculosis. Macrophages play essential roles in defense against invading pathogens, including M. tuberculosis. The study of M. tuberc...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2025-05-01
|
| Series: | BMC Immunology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12865-025-00715-6 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850190914722463744 |
|---|---|
| author | Xian-Hui Huang Yu Wang Liu-Ying Wu Ye-Lin Jiang Ling-Jie Ma Xiao-Feng Shi Xing Wang Meng-Meng Zheng Lu Tang Yong-Liang Lou Dan-Li Xie |
| author_facet | Xian-Hui Huang Yu Wang Liu-Ying Wu Ye-Lin Jiang Ling-Jie Ma Xiao-Feng Shi Xing Wang Meng-Meng Zheng Lu Tang Yong-Liang Lou Dan-Li Xie |
| author_sort | Xian-Hui Huang |
| collection | DOAJ |
| description | Abstract Mycobacterium tuberculosis (M. tuberculosis, Mtb) is a pathogenic bacterial species in the family Mycobacteriaceae and the causative agent of most cases of tuberculosis. Macrophages play essential roles in defense against invading pathogens, including M. tuberculosis. The study of M. tuberculosis-associated antigens is one of the hotspots of current research. The secreted proteins of M. tuberculosis, including early secretory antigen target 6 (ESTA6) and culture filtrate protein 10 (CFP-10), are crucial for the immunological diagnosis of tuberculosis. However, the relationship of CFP-10 alone with macrophages is still not well understood. In the present study, we report that the purified recombinant protein CFP-10 (rCFP-10) significantly enhanced the phagocytic capacity of murine macrophages. rCFP-10 induces both TNF-α and IL-6 production. Additionally, RNASeq analysis revealed that rCFP10 triggers multiple pathways involved with macrophage activation. Interestingly, neither mitochondrial reactive oxygen species nor lysosomal content had a significant difference treated with rCFP-10 in macrophages. Moreover, inhibition of the mammalian target of rapamycin (mTOR) activity was shown to significantly reverse the rCFP10-induced phagocytosis, various genes involved in lysosome acidification and TLR signaling. These findings highlight that the CFP-10 plays an essential role in the invasion of macrophages by M. tuberculosis, which is partly regulated by the mTORC2 signal pathway. |
| format | Article |
| id | doaj-art-d35acdff34074257ae0dd5cb9e4f5526 |
| institution | OA Journals |
| issn | 1471-2172 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Immunology |
| spelling | doaj-art-d35acdff34074257ae0dd5cb9e4f55262025-08-20T02:15:07ZengBMCBMC Immunology1471-21722025-05-0126111510.1186/s12865-025-00715-6mTORC2 is crucial for regulating the recombinant Mycobacterium tuberculosis CFP-10 protein-induced phagocytosis in macrophagesXian-Hui Huang0Yu Wang1Liu-Ying Wu2Ye-Lin Jiang3Ling-Jie Ma4Xiao-Feng Shi5Xing Wang6Meng-Meng Zheng7Lu Tang8Yong-Liang Lou9Dan-Li Xie10The School of Laboratory Medicine & Life Sciences, Key Laboratory of Laboratory Medicine, Wenzhou Medical University, Ministry of Education of ChinaThe School of Laboratory Medicine & Life Sciences, Key Laboratory of Laboratory Medicine, Wenzhou Medical University, Ministry of Education of ChinaThe School of Laboratory Medicine & Life Sciences, Key Laboratory of Laboratory Medicine, Wenzhou Medical University, Ministry of Education of ChinaThe School of Laboratory Medicine & Life Sciences, Key Laboratory of Laboratory Medicine, Wenzhou Medical University, Ministry of Education of ChinaThe School of Laboratory Medicine & Life Sciences, Key Laboratory of Laboratory Medicine, Wenzhou Medical University, Ministry of Education of ChinaThe School of Laboratory Medicine & Life Sciences, Key Laboratory of Laboratory Medicine, Wenzhou Medical University, Ministry of Education of ChinaThe School of Laboratory Medicine & Life Sciences, Key Laboratory of Laboratory Medicine, Wenzhou Medical University, Ministry of Education of ChinaScientific Research Center, Wenzhou Medical UniversityDepartment of Urology, Chinese PLA General HospitalThe School of Laboratory Medicine & Life Sciences, Key Laboratory of Laboratory Medicine, Wenzhou Medical University, Ministry of Education of ChinaThe School of Laboratory Medicine & Life Sciences, Key Laboratory of Laboratory Medicine, Wenzhou Medical University, Ministry of Education of ChinaAbstract Mycobacterium tuberculosis (M. tuberculosis, Mtb) is a pathogenic bacterial species in the family Mycobacteriaceae and the causative agent of most cases of tuberculosis. Macrophages play essential roles in defense against invading pathogens, including M. tuberculosis. The study of M. tuberculosis-associated antigens is one of the hotspots of current research. The secreted proteins of M. tuberculosis, including early secretory antigen target 6 (ESTA6) and culture filtrate protein 10 (CFP-10), are crucial for the immunological diagnosis of tuberculosis. However, the relationship of CFP-10 alone with macrophages is still not well understood. In the present study, we report that the purified recombinant protein CFP-10 (rCFP-10) significantly enhanced the phagocytic capacity of murine macrophages. rCFP-10 induces both TNF-α and IL-6 production. Additionally, RNASeq analysis revealed that rCFP10 triggers multiple pathways involved with macrophage activation. Interestingly, neither mitochondrial reactive oxygen species nor lysosomal content had a significant difference treated with rCFP-10 in macrophages. Moreover, inhibition of the mammalian target of rapamycin (mTOR) activity was shown to significantly reverse the rCFP10-induced phagocytosis, various genes involved in lysosome acidification and TLR signaling. These findings highlight that the CFP-10 plays an essential role in the invasion of macrophages by M. tuberculosis, which is partly regulated by the mTORC2 signal pathway.https://doi.org/10.1186/s12865-025-00715-6Mycobacterium tuberculosisCulture filtrate protein 10Mammalian target of Rapamycin complex 2Phagocytosis |
| spellingShingle | Xian-Hui Huang Yu Wang Liu-Ying Wu Ye-Lin Jiang Ling-Jie Ma Xiao-Feng Shi Xing Wang Meng-Meng Zheng Lu Tang Yong-Liang Lou Dan-Li Xie mTORC2 is crucial for regulating the recombinant Mycobacterium tuberculosis CFP-10 protein-induced phagocytosis in macrophages BMC Immunology Mycobacterium tuberculosis Culture filtrate protein 10 Mammalian target of Rapamycin complex 2 Phagocytosis |
| title | mTORC2 is crucial for regulating the recombinant Mycobacterium tuberculosis CFP-10 protein-induced phagocytosis in macrophages |
| title_full | mTORC2 is crucial for regulating the recombinant Mycobacterium tuberculosis CFP-10 protein-induced phagocytosis in macrophages |
| title_fullStr | mTORC2 is crucial for regulating the recombinant Mycobacterium tuberculosis CFP-10 protein-induced phagocytosis in macrophages |
| title_full_unstemmed | mTORC2 is crucial for regulating the recombinant Mycobacterium tuberculosis CFP-10 protein-induced phagocytosis in macrophages |
| title_short | mTORC2 is crucial for regulating the recombinant Mycobacterium tuberculosis CFP-10 protein-induced phagocytosis in macrophages |
| title_sort | mtorc2 is crucial for regulating the recombinant mycobacterium tuberculosis cfp 10 protein induced phagocytosis in macrophages |
| topic | Mycobacterium tuberculosis Culture filtrate protein 10 Mammalian target of Rapamycin complex 2 Phagocytosis |
| url | https://doi.org/10.1186/s12865-025-00715-6 |
| work_keys_str_mv | AT xianhuihuang mtorc2iscrucialforregulatingtherecombinantmycobacteriumtuberculosiscfp10proteininducedphagocytosisinmacrophages AT yuwang mtorc2iscrucialforregulatingtherecombinantmycobacteriumtuberculosiscfp10proteininducedphagocytosisinmacrophages AT liuyingwu mtorc2iscrucialforregulatingtherecombinantmycobacteriumtuberculosiscfp10proteininducedphagocytosisinmacrophages AT yelinjiang mtorc2iscrucialforregulatingtherecombinantmycobacteriumtuberculosiscfp10proteininducedphagocytosisinmacrophages AT lingjiema mtorc2iscrucialforregulatingtherecombinantmycobacteriumtuberculosiscfp10proteininducedphagocytosisinmacrophages AT xiaofengshi mtorc2iscrucialforregulatingtherecombinantmycobacteriumtuberculosiscfp10proteininducedphagocytosisinmacrophages AT xingwang mtorc2iscrucialforregulatingtherecombinantmycobacteriumtuberculosiscfp10proteininducedphagocytosisinmacrophages AT mengmengzheng mtorc2iscrucialforregulatingtherecombinantmycobacteriumtuberculosiscfp10proteininducedphagocytosisinmacrophages AT lutang mtorc2iscrucialforregulatingtherecombinantmycobacteriumtuberculosiscfp10proteininducedphagocytosisinmacrophages AT yonglianglou mtorc2iscrucialforregulatingtherecombinantmycobacteriumtuberculosiscfp10proteininducedphagocytosisinmacrophages AT danlixie mtorc2iscrucialforregulatingtherecombinantmycobacteriumtuberculosiscfp10proteininducedphagocytosisinmacrophages |