title: Local activation of coagulation factor XIII reduces systemic complications and improves the survival of mice after Streptococcus pyogenes M1 skin infection.
abstract: Coagulation is a mechanism for wound healing after injury. Several recent studies delineate an additional role of the intrinsic pathway of coagulation, also known as the contact system, in the early innate immune response against bacterial infections. In this study, we investigated the role of factor XIII (FXIII), which is activated upon coagulation induction, during Streptococcus pyogenes-mediated skin and soft tissue infections. FXIII has previously been shown to be responsible for the immobilization of bacteria within a fibrin network which may prevent systemic bacterial dissemination. In order to investigate if the FXIII-mediated entrapment of S. pyogenes also influences the disease outcome we used a murine S. pyogenes M1 skin and soft tissue infection model. Here, we demonstrate that a lack of FXIII leads to prolonged clotting times, increased signs of inflammation, and elevated bacterial dissemination. Moreover, FXIII-deficient mice show an impaired survival when compared with wildtype animals. Additionally, local reconstitution of FXIII-deficient mice with a human FXIII-concentrate (Fibrogammin®P) could reduce the systemic complications, suggesting a protective role for FXIII during early S. pyogenes skin infection. FXIII therefore might be a possible therapeutically application to support the early innate immune response during skin infections caused by S. pyogenes.
authors.affiliation: Infection Immunology Research Group, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
authors.forename: Christin
authors.initials: C
authors.lastname: Deicke
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, S-14186 Stockholm, Sweden.
authors.forename: Bhavya
authors.initials: B
authors.lastname: Chakrakodi
authors.affiliation: Mouse-pathology, Animal Experimental Unit, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
authors.forename: Marina C
authors.initials: MC
authors.lastname: Pils
authors.affiliation: Department of Preclinical Research and Development, CSL Behring GmbH, Emil-von-Behring-Strasse 76, D-35041 Marburg, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Dickneite
authors.affiliation: Center for Infectious Medicine, Department of Medicine, Karolinska Institute, Karolinska University Hospital Huddinge, S-14186 Stockholm, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Johansson
authors.affiliation: Infection Immunology Research Group, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Medina
authors.affiliation: Infection Immunology Research Group, Helmholtz Centre for Infection Research, Inhoffenstrasse 7, D-38124 Braunschweig, Germany. Electronic address: Torsten.Loof@tiho-hannover.de.
authors.forename: Torsten G
authors.initials: TG
authors.lastname: Loof
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D004195:Disease Models, Animal; D005176:Factor XIII / Q000235:genetics / Q000378:metabolism*; D005260:Female; D054884:Host-Pathogen Interactions; D007113:Immunity, Innate; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D017192:Skin Diseases, Bacterial / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D013290:Streptococcal Infections / Q000276:immunology* / Q000382:microbiology / Q000473:pathology; D013297:Streptococcus pyogenes / Q000276:immunology* / Q000472:pathogenicity; D016019:Survival Analysis
chemical_list: D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; C014689:streptococcal M protein; D005176:Factor XIII
keywords: Coagulation; Factor XIII; Innate immunity; Skin infection; Streptococcus pyogenes