A Study on the Inflammatory Response of the Brain in Neurosyphilis
Abstract Neurosyphilis (NS) is a clinical condition caused by infection of the central nervous system (CNS) by Treponema pallidum (Tp) that can lead to asymptomatic meningitis and more serious neurological diseases, such as dementia and blindness. However, current studies on the pathogenesis of NS a...
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| Format: | Article |
| Language: | English |
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Wiley
2025-02-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202406971 |
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| author | Qiyu Zhang Jie Ma Jia Zhou Hanlin Zhang Mansheng Li Huizi Gong Yujie Wang Heyi Zheng Jun Li Ling Leng |
| author_facet | Qiyu Zhang Jie Ma Jia Zhou Hanlin Zhang Mansheng Li Huizi Gong Yujie Wang Heyi Zheng Jun Li Ling Leng |
| author_sort | Qiyu Zhang |
| collection | DOAJ |
| description | Abstract Neurosyphilis (NS) is a clinical condition caused by infection of the central nervous system (CNS) by Treponema pallidum (Tp) that can lead to asymptomatic meningitis and more serious neurological diseases, such as dementia and blindness. However, current studies on the pathogenesis of NS are limited. Here, through the integration analysis of proteomics and single‐cell transcriptomics, Toll‐like/NF‐κB signaling is identified as the key pathway involved in CNS damage caused by Tp. Moreover, monocyte‐derived macrophages are key cells involved in the inflammatory response to Tp in the CNS of NS patients. In addition, it is found that inflammatory cells in peripheral blood may cause neurological damage through disruption of the blood‒brain barrier (BBB) in individuals with NS. Notably, activation of the Toll‐like/NF‐κB signaling pathway, as well as dysregulation of neural function, is likewise validated in an in vitro NS brain organoid model. In conclusion, the results revealed the mechanisms of inflammation‐mediated brain injury in Tp‐induced NS and provided new ideas for the clinical treatment of Tp infection. |
| format | Article |
| id | doaj-art-904e867bfffb482ab20ffbcddf524306 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-904e867bfffb482ab20ffbcddf5243062025-02-04T13:14:54ZengWileyAdvanced Science2198-38442025-02-01125n/an/a10.1002/advs.202406971A Study on the Inflammatory Response of the Brain in NeurosyphilisQiyu Zhang0Jie Ma1Jia Zhou2Hanlin Zhang3Mansheng Li4Huizi Gong5Yujie Wang6Heyi Zheng7Jun Li8Ling Leng9Stem cell and Regenerative Medicine Lab Institute of Clinical Medicine State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730 ChinaState Key Laboratory of Medical Proteomics Beijing Proteome Research Center National Center for Protein Sciences (Beijing) Beijing Institute of Lifeomics Beijing 102206 ChinaStem cell and Regenerative Medicine Lab Institute of Clinical Medicine State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730 ChinaDepartment of Dermatology Institute of Clinical Medicine State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College National Clinical Research Center for Dermatologic and Immunologic Diseases Beijing 100730 ChinaState Key Laboratory of Medical Proteomics Beijing Proteome Research Center National Center for Protein Sciences (Beijing) Beijing Institute of Lifeomics Beijing 102206 ChinaDepartment of Dermatology Institute of Clinical Medicine State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College National Clinical Research Center for Dermatologic and Immunologic Diseases Beijing 100730 ChinaStem cell and Regenerative Medicine Lab Institute of Clinical Medicine State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730 ChinaDepartment of Dermatology Institute of Clinical Medicine State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College National Clinical Research Center for Dermatologic and Immunologic Diseases Beijing 100730 ChinaDepartment of Dermatology Institute of Clinical Medicine State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College National Clinical Research Center for Dermatologic and Immunologic Diseases Beijing 100730 ChinaStem cell and Regenerative Medicine Lab Institute of Clinical Medicine State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Beijing 100730 ChinaAbstract Neurosyphilis (NS) is a clinical condition caused by infection of the central nervous system (CNS) by Treponema pallidum (Tp) that can lead to asymptomatic meningitis and more serious neurological diseases, such as dementia and blindness. However, current studies on the pathogenesis of NS are limited. Here, through the integration analysis of proteomics and single‐cell transcriptomics, Toll‐like/NF‐κB signaling is identified as the key pathway involved in CNS damage caused by Tp. Moreover, monocyte‐derived macrophages are key cells involved in the inflammatory response to Tp in the CNS of NS patients. In addition, it is found that inflammatory cells in peripheral blood may cause neurological damage through disruption of the blood‒brain barrier (BBB) in individuals with NS. Notably, activation of the Toll‐like/NF‐κB signaling pathway, as well as dysregulation of neural function, is likewise validated in an in vitro NS brain organoid model. In conclusion, the results revealed the mechanisms of inflammation‐mediated brain injury in Tp‐induced NS and provided new ideas for the clinical treatment of Tp infection.https://doi.org/10.1002/advs.202406971blood‒brain barrierinflammation‐mediated brain injuryneurosyphilisproteomicssingle‐cell transcriptomics |
| spellingShingle | Qiyu Zhang Jie Ma Jia Zhou Hanlin Zhang Mansheng Li Huizi Gong Yujie Wang Heyi Zheng Jun Li Ling Leng A Study on the Inflammatory Response of the Brain in Neurosyphilis Advanced Science blood‒brain barrier inflammation‐mediated brain injury neurosyphilis proteomics single‐cell transcriptomics |
| title | A Study on the Inflammatory Response of the Brain in Neurosyphilis |
| title_full | A Study on the Inflammatory Response of the Brain in Neurosyphilis |
| title_fullStr | A Study on the Inflammatory Response of the Brain in Neurosyphilis |
| title_full_unstemmed | A Study on the Inflammatory Response of the Brain in Neurosyphilis |
| title_short | A Study on the Inflammatory Response of the Brain in Neurosyphilis |
| title_sort | study on the inflammatory response of the brain in neurosyphilis |
| topic | blood‒brain barrier inflammation‐mediated brain injury neurosyphilis proteomics single‐cell transcriptomics |
| url | https://doi.org/10.1002/advs.202406971 |
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