Beyond Hemostasis: Platelets' Multifaceted Functions in Immune Responses

Platelets are anucleated cell fragments representing the second most abundant blood element in circulation, with approximately 100 billion new platelets released from the bone marrow daily in a healthy individual. For over a century, their hemostatic role was considered their primary function; however, the past few decades of research have revealed significant immunological functions in both innate and adaptive immunity. Through the release of mediators stored in platelet granules and the expression and realignment of a diverse array of surface receptors, platelets influence immune cells while simultaneously recognizing, reacting to, and phagocytosing offending pathogens such as viruses and bacteria. Their activation initiates signaling cascades that either amplify platelet responses or drive the activation, recruitment, migration, and maturation of immune cells to sites of infection. This narrative review synthesizes platelet biology, receptor signaling, granule physiology, and platelet interactions with innate and adaptive immune cells to provide an integrated perspective on platelet immunologic function. We examine platelets as frontline immune sentinels and evaluate their capacity to regulate both innate and adaptive immune responses, detailing specific receptors and granule contents as the mechanistic foundation for their immunologic roles. We further explore the molecular mechanisms by which platelets interact with pathogens and immune cells to drive pathogen clearance, inflammation modulation, and the interplay between thrombosis and immunity, including their contributions to chronic inflammatory disease and tumorigenesis.