Platelets at the Interface between Hemostasis and Innate Immunity

Summary Pathogenic microorganisms often cause severe systemic infectious diseases if they reach the bloodstream. Innate immune defense mechanisms are very fast and one of the most effective weapons against infections. Platelets, known as primary actors in hemostasis and thrombin generation, maintain, like leukocytes, multiple functions of innate defense mechanisms: pathogen sequestration by clotting, pathogen clearance by phagocytosis, pathogen killing by secretion of antimicrobial substances, and complement activation. Interactions between platelets and parasitic protozoa, viruses, pathogenic fungi, or bacteria trigger platelet cytotoxicity. Platelets also modulate the inflammatory response after infections by pathogens. The formation of platelet-leukocyte associates in the circulation and the release of platelet-derived inflammatory chemokines and cytokines augment the (pro)inflammatory activity of leukocytes and vascular cells. Immobilized on the damaged vessel wall, activated platelets capture leukocytes from the circulation and attract them to the inflamed tissue. In addition, it has been shown that platelets play important roles in adaptive immunity. They regulate the classical B/T-cell- and immunglobulin-mediated immune response via CD40/ligand-CD40 interactions. A better understanding of the new central role of platelets as defense cells is required for the development of efficient therapeutic strategies against infectious complications and resistance to antibiotics.