Platelet-Neutrophil Interplay: Insights Into Neutrophil Extracellular Trap (NET)-Driven Coagulation in Infection

Well established for their central role in hemostasis, platelets have increasingly been appreciated as immune cells in recent years. This emerging role should not come as a surprise as the central immune cells of invertebrates, hemocytes, are able to phagocytose, secrete soluble mediators and promote coagulation of hemolymph, blurring the line between immunity and hemostasis. The undeniable evolutionary link between coagulation and immunity becomes even clearer as the role of platelets in inflammation is better understood. Platelets exert a range of immune-related functions, many of which involve an intimate interplay with leukocytes. Platelets promote leukocyte recruitment via endothelial activation and can serve as "landing pads" for leukocytes, facilitating cellular adhesion in vascular beds devoid of classic adhesion molecules. Moreover, platelets enhance leukocyte function both through direct interactions and through release of soluble mediators. Among neutrophil-platelets interactions, the modulation of neutrophil extracellular traps (NETs) is of great interest. Platelets have been shown to induce NET formation; and, in turn, NET components further regulate platelet and neutrophil function. While NETs have been shown to ensnare and kill pathogens, they also initiate coagulation via thrombin activation. In fact, increased NET formation has been associated with hypercoagulability in septic patients as well as in chronic vascular disorders. This review will delve into current knowledge of platelet-neutrophil interactions, with a focus on NET-driven coagulation, in the context of infectious diseases. A better understanding of these mechanisms will shed a light on the therapeutic potential of uncoupling immunity and coagulation through targeting of NETs.