The helminth product ES-62 protects against septic shock via Toll-like receptor 4-dependent autophagosomal degradation of the adaptor MyD88
Sepsis is one of the most challenging health problems worldwide. Here we found that phagocytes from patients with sepsis had considerable upregulation of Toll-like receptor 4 (TLR4) and TLR2; however, shock-inducing inflammatory responses mediated by these TLRs were inhibited by ES-62, an immunomodu...
| Main Authors: | , , , , , , , , , |
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| Format: | Journal Article |
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Nature Publishing Group
2011
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| Online Access: | http://hdl.handle.net/20.500.11937/51243 |
| _version_ | 1848758649451708416 |
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| author | Puneet, P. McGrath, M. Tay, H. Al-Riyami, L. Rzepecka, J. Moochhala, S. Pervaiz, Shazib Harnett, M. Harnett, W. Melendez, A. |
| author_facet | Puneet, P. McGrath, M. Tay, H. Al-Riyami, L. Rzepecka, J. Moochhala, S. Pervaiz, Shazib Harnett, M. Harnett, W. Melendez, A. |
| author_sort | Puneet, P. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Sepsis is one of the most challenging health problems worldwide. Here we found that phagocytes from patients with sepsis had considerable upregulation of Toll-like receptor 4 (TLR4) and TLR2; however, shock-inducing inflammatory responses mediated by these TLRs were inhibited by ES-62, an immunomodulator secreted by the filarial nematode Acanthocheilonema viteae. ES-62 subverted TLR4 signaling to block TLR2- and TLR4-driven inflammatory responses via autophagosome-mediated downregulation of the TLR adaptor-transducer MyD88. In vivo, ES-62 protected mice against endotoxic and polymicrobial septic shock by TLR4-mediated induction of autophagy and was protective even when administered after the induction of sepsis. Given that the treatments for septic shock at present are inadequate, the autophagy-dependent mechanism of action by ES-62 might form the basis for urgently needed therapeutic intervention against this life-threatening condition. © 2011 Nature America, Inc. All rights reserved. |
| first_indexed | 2025-11-14T09:47:21Z |
| format | Journal Article |
| id | curtin-20.500.11937-51243 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T09:47:21Z |
| publishDate | 2011 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-512432017-09-13T15:34:26Z The helminth product ES-62 protects against septic shock via Toll-like receptor 4-dependent autophagosomal degradation of the adaptor MyD88 Puneet, P. McGrath, M. Tay, H. Al-Riyami, L. Rzepecka, J. Moochhala, S. Pervaiz, Shazib Harnett, M. Harnett, W. Melendez, A. Sepsis is one of the most challenging health problems worldwide. Here we found that phagocytes from patients with sepsis had considerable upregulation of Toll-like receptor 4 (TLR4) and TLR2; however, shock-inducing inflammatory responses mediated by these TLRs were inhibited by ES-62, an immunomodulator secreted by the filarial nematode Acanthocheilonema viteae. ES-62 subverted TLR4 signaling to block TLR2- and TLR4-driven inflammatory responses via autophagosome-mediated downregulation of the TLR adaptor-transducer MyD88. In vivo, ES-62 protected mice against endotoxic and polymicrobial septic shock by TLR4-mediated induction of autophagy and was protective even when administered after the induction of sepsis. Given that the treatments for septic shock at present are inadequate, the autophagy-dependent mechanism of action by ES-62 might form the basis for urgently needed therapeutic intervention against this life-threatening condition. © 2011 Nature America, Inc. All rights reserved. 2011 Journal Article http://hdl.handle.net/20.500.11937/51243 10.1038/ni.2004 Nature Publishing Group restricted |
| spellingShingle | Puneet, P. McGrath, M. Tay, H. Al-Riyami, L. Rzepecka, J. Moochhala, S. Pervaiz, Shazib Harnett, M. Harnett, W. Melendez, A. The helminth product ES-62 protects against septic shock via Toll-like receptor 4-dependent autophagosomal degradation of the adaptor MyD88 |
| title | The helminth product ES-62 protects against septic shock via Toll-like receptor 4-dependent autophagosomal degradation of the adaptor MyD88 |
| title_full | The helminth product ES-62 protects against septic shock via Toll-like receptor 4-dependent autophagosomal degradation of the adaptor MyD88 |
| title_fullStr | The helminth product ES-62 protects against septic shock via Toll-like receptor 4-dependent autophagosomal degradation of the adaptor MyD88 |
| title_full_unstemmed | The helminth product ES-62 protects against septic shock via Toll-like receptor 4-dependent autophagosomal degradation of the adaptor MyD88 |
| title_short | The helminth product ES-62 protects against septic shock via Toll-like receptor 4-dependent autophagosomal degradation of the adaptor MyD88 |
| title_sort | helminth product es-62 protects against septic shock via toll-like receptor 4-dependent autophagosomal degradation of the adaptor myd88 |
| url | http://hdl.handle.net/20.500.11937/51243 |