Sepsis is a leading cause of death in hospitals. The dysregulation of blood clotting pathways contributes to septic pathology. Fibrin, a product of blood clotting pathways, physically staunches blood loss during trauma. Fibrin also is produced during sepsis and many immune responses, including those that combat infection, reject transplants, and cause autoimmune diseases. In these settings, fibrin is thought to exacerbate pathology by starving tissues of oxygen and amplifying inflammation. However, we found that fibrin performs an essential host-protective function during infections including protozoan Toxoplasma gondii, Gram-positive bacterium Listeria monocytogenes, Gram-negative bacterium Yersinia enterocolitica and Yersinia pestis. We found that fibrin functions protectively during infections by limiting hemorrhagic pathology, suppressing bacterial growth or helping neutrophils withstand bacteria encounters. Our observations help to explain why fully antagonizing blood clotting processes does not improve survival for septic patients. We hypothesize that suppresses pathology induced by dysregulated blood clotting pathways while maintains and exploits the protective functions of fibrin will lead to new therapeutic strategies.
Now we are working to define how fibrin assists and impairs immune defense against bacterial infection. Ultimately, we are hoping to use this knowledge to engineer fibrin-based sepsis therapeutics that will attenuate pathology while maintaining protective functions.