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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.

Authors

Lorena Zuliani-Alvarez

Anna M. Marzeda

Claire Deligne

Anja Schwenzer

Fiona E. McCann

Brian D. Marsden

Anna M. Piccinini

Kim S. Midwood



Abstract

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.

Journal Article Type Article
Journal Nature Communications
Electronic ISSN 2041-1723
Publisher Nature Publishing Group
Peer Reviewed Peer Reviewed
Volume 8
Issue 1
APA6 Citation Zuliani-Alvarez, L., Marzeda, A. M., Deligne, C., Schwenzer, A., McCann, F. E., Marsden, B. D., …Midwood, K. S. (in press). Mapping tenascin-C interaction with toll-like receptor 4 reveals a new subset of endogenous inflammatory triggers. Nature Communications, 8(1), https://doi.org/10.1038/s41467-017-01718-7
DOI https://doi.org/10.1038/s41467-017-01718-7
Publisher URL https://www.nature.com/articles/s41467-017-01718-7
Copyright Statement Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0

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Zuliani et al Nat Commun 2017.pdf (6.1 Mb)
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Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0


Zuliani et al Nat Commun 2017 Suppl Mat.pdf (1.6 Mb)
PDF

Copyright Statement
Copyright information regarding this work can be found at the following address: http://creativecommons.org/licenses/by/4.0





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