Coagulation, an ancestral serine protease cascade, exerts a novel function in early immune defense.

摘要

Phylogenetically conserved serine protease cascades play an important role in invertebrate and vertebrate immunity. The mammalian coagulation system can be traced back some 400 million years and it shares homology with ancestral serine proteinase cascades involved for instance in Toll receptor signaling in insects and release of antimicrobial peptides during hemolymph clotting. Here we show that bacteria-evoked induction of coagulation leads to an immobilization and killing of Streptococcus pyogenes bacteria inside the clot. The entrapment is mediated via crosslinking bacteria to fibrin fibers by the action of coagulation factor XIII (fXIII), an evolutionarily conserved transglutaminase. In a streptococcal skin infection model, fXIII(-/-) mice develop severe signs of pathologic inflammation at the local site of infection and fXIII-treatment of wildtype animals dampens bacterial dissemination during early infection. Bacterial killing and crosslinking to fibrin networks was also detected in tissue biopsies from patients with streptococcal necrotizing fasciitis supporting the concept that coagulation is part of the early innate immune system.