Dengue virus – elicited tryptase induces endothelial permeability and shock
Dengue virus (DENV) infection causes a characteristic pathology in humans involving dysregulation of the vascular system. In some patients with dengue hemorrhagic fever (DHF), vascular pathology can become severe, resulting in extensive microvascular permeability and plasma leakage into tissues and...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
| Published: |
2020
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| Online Access: | https://hdl.handle.net/10356/142486 |
| _version_ | 1826125320123580416 |
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| author | Rathore, Abhay P. S. Mantri, Chinmay Kumar Aman, Siti A. B. Syenina, Ayesa Ooi, Justin Jagaraj, Cyril J. Goh, Chi Ching Tissera, Hasitha Wilder-Smith, Annelies Ng, Lai Guan Gubler, Duane J. St. John, Ashley L. |
| author2 | School of Biological Sciences |
| author_facet | School of Biological Sciences Rathore, Abhay P. S. Mantri, Chinmay Kumar Aman, Siti A. B. Syenina, Ayesa Ooi, Justin Jagaraj, Cyril J. Goh, Chi Ching Tissera, Hasitha Wilder-Smith, Annelies Ng, Lai Guan Gubler, Duane J. St. John, Ashley L. |
| author_sort | Rathore, Abhay P. S. |
| collection | NTU |
| description | Dengue virus (DENV) infection causes a characteristic pathology in humans involving dysregulation of the vascular system. In some patients with dengue hemorrhagic fever (DHF), vascular pathology can become severe, resulting in extensive microvascular permeability and plasma leakage into tissues and organs. Mast cells (MCs), which line blood vessels and regulate vascular function, are able to detect DENV in vivo and promote vascular leakage. Here, we showed that an MC-derived protease, tryptase, is consequential for promoting vascular permeability during DENV infection through inducing breakdown of endothelial cell tight junctions. Injected tryptase alone was sufficient to induce plasma loss from the circulation and hypovolemic shock in animals. A potent tryptase inhibitor, nafamostat mesylate, blocked DENV-induced vascular leakage in vivo. Importantly, in 2 independent human dengue cohorts, tryptase levels correlated with the grade of DHF severity. This study defines an immune mechanism by which DENV can induce vascular pathology and shock. |
| first_indexed | 2024-10-01T06:34:43Z |
| format | Journal Article |
| id | ntu-10356/142486 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:34:43Z |
| publishDate | 2020 |
| record_format | dspace |
| spelling | ntu-10356/1424862023-02-28T17:07:35Z Dengue virus – elicited tryptase induces endothelial permeability and shock Rathore, Abhay P. S. Mantri, Chinmay Kumar Aman, Siti A. B. Syenina, Ayesa Ooi, Justin Jagaraj, Cyril J. Goh, Chi Ching Tissera, Hasitha Wilder-Smith, Annelies Ng, Lai Guan Gubler, Duane J. St. John, Ashley L. School of Biological Sciences Lee Kong Chian School of Medicine (LKCMedicine) Singapore Immunology Network, A*STAR Science::Biological sciences Dengue Virus (DENV) Dengue Hemorrhagic Fever (DHF) Dengue virus (DENV) infection causes a characteristic pathology in humans involving dysregulation of the vascular system. In some patients with dengue hemorrhagic fever (DHF), vascular pathology can become severe, resulting in extensive microvascular permeability and plasma leakage into tissues and organs. Mast cells (MCs), which line blood vessels and regulate vascular function, are able to detect DENV in vivo and promote vascular leakage. Here, we showed that an MC-derived protease, tryptase, is consequential for promoting vascular permeability during DENV infection through inducing breakdown of endothelial cell tight junctions. Injected tryptase alone was sufficient to induce plasma loss from the circulation and hypovolemic shock in animals. A potent tryptase inhibitor, nafamostat mesylate, blocked DENV-induced vascular leakage in vivo. Importantly, in 2 independent human dengue cohorts, tryptase levels correlated with the grade of DHF severity. This study defines an immune mechanism by which DENV can induce vascular pathology and shock. NMRC (Natl Medical Research Council, S’pore) Published version 2020-06-23T01:16:49Z 2020-06-23T01:16:49Z 2019 Journal Article Rathore, A. P. S., Mantri, C. K., Aman, S. A. B., Syenina, A., Ooi, J., Jagaraj, C. J., . . . St. John, A. L. (2019). Dengue virus – elicited tryptase induces endothelial permeability and shock. The Journal of Clinical Investigation, 129(10), 4180-4193. doi:10.1172/JCI128426 0021-9738 https://hdl.handle.net/10356/142486 10.1172/JCI128426 31265436 2-s2.0-85069269851 10 129 4180 4193 en The Journal of Clinical Investigation © 2019 American Society for Clinical Investigation. This is an open-access article distributed under the terms of the Creative Commons Attribution License. application/pdf |
| spellingShingle | Science::Biological sciences Dengue Virus (DENV) Dengue Hemorrhagic Fever (DHF) Rathore, Abhay P. S. Mantri, Chinmay Kumar Aman, Siti A. B. Syenina, Ayesa Ooi, Justin Jagaraj, Cyril J. Goh, Chi Ching Tissera, Hasitha Wilder-Smith, Annelies Ng, Lai Guan Gubler, Duane J. St. John, Ashley L. Dengue virus – elicited tryptase induces endothelial permeability and shock |
| title | Dengue virus – elicited tryptase induces endothelial permeability and shock |
| title_full | Dengue virus – elicited tryptase induces endothelial permeability and shock |
| title_fullStr | Dengue virus – elicited tryptase induces endothelial permeability and shock |
| title_full_unstemmed | Dengue virus – elicited tryptase induces endothelial permeability and shock |
| title_short | Dengue virus – elicited tryptase induces endothelial permeability and shock |
| title_sort | dengue virus elicited tryptase induces endothelial permeability and shock |
| topic | Science::Biological sciences Dengue Virus (DENV) Dengue Hemorrhagic Fever (DHF) |
| url | https://hdl.handle.net/10356/142486 |
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