Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers

Zuliani-Alvarez, Lorena; Marzeda, Anna M.; Deligne, Claire; Schwenzer, Anja; McCann, Fiona E.; Marsden, Brian D.; Piccinini, Anna M.; Midwood, Kim S.

Abstract

© 2017 The Author(s). 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, while 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.

Citation

Zuliani-Alvarez, L., Marzeda, A. M., Deligne, C., Schwenzer, A., McCann, F. E., Marsden, B. D., …Midwood, K. S. (2017). Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers. Nature Communications, 8(1), Article 1595. https://doi.org/10.1038/s41467-017-01718-7

• Journal Article Type: Article
• Acceptance Date: Oct 5, 2017
• Online Publication Date: Nov 17, 2017
• Publication Date: Dec 1, 2017
• Deposit Date: Nov 20, 2017
• Publicly Available Date: Nov 20, 2017
• Journal: Nature Communications
• Electronic ISSN: 2041-1723
• Publisher: Nature Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 8
• Issue: 1
• Article Number: 1595
• DOI: https://doi.org/10.1038/s41467-017-01718-7
• Public URL: https://nottingham-repository.worktribe.com/output/895792
• Publisher URL: https://www.nature.com/articles/s41467-017-01718-7