Department of Microbiology & Immunology Seminar: “(Pro)thrombin Regulates Adaptive Immunity in the Context of Chronic Viral Infection”

Speaker:
Joseph Palumbo, MD
Director, Comprehensive Thrombophilia Center
Co-Director of the Hemostasis Thrombosis Laboratory (HTL)
Professor, Department of Pediatrics
Cincinnati Children’s Hospital Medical Center

Location: Med-Dent NE301 or via Zoom

Abstract:
Thrombin is the central regulator of the hemostatic system with the capacity to proteolytically activate more than a dozen substrates, including pro- and anti-coagulant hemostatic proteases and protease-activated receptors (PARs) expressed by a myriad of cell types. Thrombin also regulates the activation and release of proteins involved in immune regulation, including fibrinogen, osteopontin, IL-1a and TGF-b1. Previous studies from our laboratory have shown that thrombin regulates multiple innate immune processes in the context of cancer progression, inflammatory colitis, and inflammation associated tumorigenesis.

The primary focus of my talk today will be a novel for (pro)thrombin in the regulation of adaptive immune processes related to chronic viral infection with lymphocytic choriomeningitis virus (LCMV) clone 13 strain. In this context, we showed that prothrombin depletion resulted in an unexpected mortality following infection with LCMV clone 13. We further show that (pro)thrombin supports survival in this experimental setting by a mechanism linked to CD8+ T cell functions and limits the development of a severe hemolytic anemia.