Cleavage of fibrinogen by proteinases elicits allergic responses through toll-like receptor 4

Valentine Ongeri Millien, Wen Lu, Joanne Shaw, Xiaoyi Yuan, Garbo Mak, Luz Roberts, Li Zhen Song, J. Morgan Knight, Chad J. Creighton, Amber Luong, Farrah Kheradmand, David Corry

Research output: Contribution to journalArticle

134 Scopus citations

Abstract

Proteinases and the innate immune receptor Toll-like receptor 4 (TLR4) are essential for expression of allergic inflammation and diseases such as asthma. A mechanism that links these inflammatory mediators is essential for explaining the fundamental basis of allergic disease but has been elusive. Here, we demonstrate that TLR4 is activated by airway proteinase activity to initiate both allergic airway disease and antifungal immunity. These outcomes were induced by proteinase cleavage of the clotting protein fibrinogen, yielding fibrinogen cleavage products that acted as TLR4 ligands on airway epithelial cells and macrophages. Thus, allergic airway inflammation represents an antifungal defensive strategy that is driven by fibrinogen cleavage and TLR4 activation. These findings clarify the molecular basis of allergic disease and suggest new therapeutic strategies.

Original languageEnglish (US)
Pages (from-to)792-796
Number of pages5
JournalScience
Volume341
Issue number6147
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • General

Fingerprint Dive into the research topics of 'Cleavage of fibrinogen by proteinases elicits allergic responses through toll-like receptor 4'. Together they form a unique fingerprint.

Cite this