Infection-stimulated fibrin deposition controls hemorrhage and limits hepatic bacterial growth during listeriosis
| Autor: | Kiera N. Berggren, Stephen T. Smiley, Lawrence W. Kummer, Isis K. Mullarky, Frank M. Szaba, Lawrence L. Johnson, Wangxue Chen, Michelle A. Parent |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Immunology
Nitric Oxide Synthase Type II Hemorrhage Biology medicine.disease_cause Fibrinogen Microbiology Fibrin Peritoneal cavity Interferon-gamma Mice Listeria monocytogenes medicine Extracellular Animals Listeriosis RNA Messenger Peritoneal Infection Host Response and Inflammation Tumor Necrosis Factor-alpha Mice Inbred C57BL Infectious Diseases medicine.anatomical_structure Coagulation Liver biology.protein Parasitology Tumor necrosis factor alpha Nitric Oxide Synthase medicine.drug |
| Zdroj: | Infection and immunity. 73(7) |
| ISSN: | 0019-9567 |
| Popis: | Bacterial infections are major causes of human mortality. The activation of coagulation pathways leading to the deposition of insoluble fibrin frequently accompanies bacterial infection, and much attention has focused upon the pathological attributes of infection-stimulated fibrin deposition. Nevertheless, here we present conclusive evidence that infection-stimulated fibrin deposition can perform critical protective functions during bacterial infection. Specifically, we demonstrate that coagulation-impaired fibrin(ogen)-deficient mice, in comparison with genetically matched control mice, display increased mortality upon peritoneal infection with the gram-positive facultative intracellular bacteriumListeria monocytogenes. To distinguish effects of fibrinogen from those of fibrin, we treat wild-type mice with warfarin, an anticoagulant that suppresses fibrin formation without impacting fibrinogen levels. Warfarin treatment exacerbates listeriosis, suggesting that fibrin is the key mediator of protection. With regard to the underlying protective mechanisms, we demonstrate that fibrin(ogen) suppresses anemia, reduces hemorrhagic pathology, and limits bacterial growth during listeriosis. Despite confirming a prior report that fibrin(ogen) promotes the peritoneal clearance of the extracellular bacteriumStaphylococcal aureus, we demonstrate that fibrin(ogen) plays little role in controlling peritoneal numbers ofL. monocytogenesbacteria or the dissemination ofL. monocytogenesbacteria from the peritoneal cavity. Rather, fibrin(ogen) primarily limits the growth of these intracellular bacteria within hepatic tissue. While the pathological potential of excessive infection-stimulated fibrin deposition is well appreciated, our findings reveal that fibrin can function protectively, via multiple mechanisms, during bacterial infection. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|