title: Coagulation, an ancestral serine protease cascade, exerts a novel function in early immune defense.
abstract: 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 shares homology with ancestral serine proteinase cascades that are involved in, for example, Toll receptor signaling in insects and release of antimicrobial peptides during hemolymph clotting. In the present study, we show that the induction of coagulation by bacteria leads to immobilization and killing of Streptococcus pyogenes bacteria inside the clot. The entrapment is mediated via cross-linking of bacteria to fibrin fibers by the action of coagulation factor XIII (fXIII), an evolutionarily conserved transglutaminase. In a streptococcal skin infection model, fXIII(-/-) mice developed severe signs of pathologic inflammation at the local site of infection, and fXIII treatment of wild-type animals dampened bacterial dissemination during early infection. Bacterial killing and cross-linking 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.
authors: Department of Clinical Sciences, Biomedical Center, Lund University, Lund, Sweden.
authors: Torsten G
authors: TG
authors: Loof
authors: Matthias
authors: M
authors: Mörgelin
authors: Linda
authors: L
authors: Johansson
authors: Sonja
authors: S
authors: Oehmcke
authors: Anders I
authors: AI
authors: Olin
authors: Gerhard
authors: G
authors: Dickneite
authors: Anna
authors: A
authors: Norrby-Teglund
authors: Ulrich
authors: U
authors: Theopold
authors: Heiko
authors: H
authors: Herwald