Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers
Pattern recognition underpins innate immunity; the accurate identification of danger, including infection, injury or tumor, is key to an appropriately targeted immune response. Pathogen detection is increasingly well defined mechanistically, but the discrimination of endogenous inflammatory trigge...
| Main Authors: | , , , , , , , |
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| Format: | Journal article |
| Published: |
Springer Nature
2017
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| _version_ | 1797071416796905472 |
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| author | Zuliani-Alvarez, L Marzeda, A Deligne, C Schwenzer, A McCann, F Marsden, B Piccinini, A Midwood, K |
| author_facet | Zuliani-Alvarez, L Marzeda, A Deligne, C Schwenzer, A McCann, F Marsden, B Piccinini, A Midwood, K |
| author_sort | Zuliani-Alvarez, L |
| collection | OXFORD |
| description | Pattern recognition underpins innate immunity; the accurate identification of danger, including infection, injury or tumor, is key to an appropriately targeted immune response. Pathogen detection is increasingly well defined mechanistically, but the discrimination of endogenous inflammatory triggers remains unclear. Tenascin-C, a matrix protein induced upon tissue damage and expressed by tumors, activates toll-like receptor 4 (TLR4) mediated sterile inflammation. Here, we map three sites within tenascin-C that directly and cooperatively interact with TLR4. We also identify a conserved inflammatory epitope in related proteins from diverse families, and demonstrate that its presence targets molecules for TLR detection, whilst its absence enables escape of innate immune surveillance. These data reveal a unique molecular code that defines endogenous proteins as inflammatory stimuli by marking them for recognition by TLRs. |
| first_indexed | 2024-03-06T22:52:56Z |
| format | Journal article |
| id | oxford-uuid:5f6575e9-0077-4cc2-a05d-1cc1bd7a35ab |
| institution | University of Oxford |
| last_indexed | 2024-03-06T22:52:56Z |
| publishDate | 2017 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:5f6575e9-0077-4cc2-a05d-1cc1bd7a35ab2022-03-26T17:46:43ZMapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggersJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:5f6575e9-0077-4cc2-a05d-1cc1bd7a35abSymplectic Elements at OxfordSpringer Nature2017Zuliani-Alvarez, LMarzeda, ADeligne, CSchwenzer, AMcCann, FMarsden, BPiccinini, AMidwood, KPattern recognition underpins innate immunity; the accurate identification of danger, including infection, injury or tumor, is key to an appropriately targeted immune response. Pathogen detection is increasingly well defined mechanistically, but the discrimination of endogenous inflammatory triggers remains unclear. Tenascin-C, a matrix protein induced upon tissue damage and expressed by tumors, activates toll-like receptor 4 (TLR4) mediated sterile inflammation. Here, we map three sites within tenascin-C that directly and cooperatively interact with TLR4. We also identify a conserved inflammatory epitope in related proteins from diverse families, and demonstrate that its presence targets molecules for TLR detection, whilst its absence enables escape of innate immune surveillance. These data reveal a unique molecular code that defines endogenous proteins as inflammatory stimuli by marking them for recognition by TLRs. |
| spellingShingle | Zuliani-Alvarez, L Marzeda, A Deligne, C Schwenzer, A McCann, F Marsden, B Piccinini, A Midwood, K Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers |
| title | Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers |
| title_full | Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers |
| title_fullStr | Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers |
| title_full_unstemmed | Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers |
| title_short | Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers |
| title_sort | mapping tenascin c interaction with toll like receptor 4 reveals a new subset of endogenous inflammatory triggers |
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