Coagulation, PARs and Host Defense

The clotting system is activated during infection and plays a role on host defense. Formation of a clot reduces dissemination of the pathogen and fibrin enhances the activation of macrophages. Surprisingly, we observed that PAR1 deficient mice exhibited increased cardiac injury after infection with Coxsackievirus B3 (CVB3) infection.  Similar results were observed in wild-type mice that received an anti-TF antibody or a thrombin inhibitor.  Further studies revealed that activation of PAR1 on cardiac fibroblasts enhanced TLR3-dependent expression of IFNgamma expression. We have also found that PAR1 deficient mice exhibit increased mortality after infection with influenza virus A (IAV). These studies indicate that the TF-thrombin-PAR1 pathway contributes to the innate immune response to single-stranded viruses (Figure 8).