Selective cleavage of fibrinogen by diverse proteinases initiates innate allergic and antifungal immunity through CD11b.

ABSTRACT: Proteinases are essential drivers of allergic airway disease and innate antifungal immunity in part through their ability cleave the clotting factor fibrinogen (FBG) into fibrinogen cleavage products (FCPs) that signal through Toll-like receptor 4 (TLR4). However, the mechanism by which FCPs engage TLR4 remains unknown. Here, we show that the proteinases from Aspergillus melleus (PAM) and other allergenic organisms rapidly hydrolyze FBG to yield relatively few FCPs that drive distinct antifungal mechanisms through TLR4. Functional FCPs, termed cryptokines, were characterized by rapid loss of the FBG α chain with substantial preservation of the β and γ chains, including a γ chain sequence (Fibγ390-396) that binds the integrin Mac-1 (CD11b/CD18). PAM-derived cryptokines could be gener

SUBMITTER: Landers CT 

PROVIDER: S-EPMC6552423 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature