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_name
Nat Communjournal_title
Nature communicationsauthors
Zuliani-Alvarez L,Marzeda AM,Deligne C,Schwenzer A,McCann FE,Marsden BD,Piccinini AM,Midwood KSdoi
10.1038/s41467-017-01718-7subject
Has Abstractpub_date
2017-11-17 00:00:00pages
1595issue
1issn
2041-1723pii
10.1038/s41467-017-01718-7journal_volume
8pub_type
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