Neonatal platelets differentiate monocytes to a myeloid-derived suppressor cell phenotype.

Adult platelets are relatively enriched in immune-related molecules compared with neonatal platelets, but neonatal platelets express some growth factors and enzymes at comparatively higher levels. This makes a prediction of platelet-immune cell interaction outcomes in neonates a challenge, as they are likely dependent on the cell type and tissue environment at the time of injury or infection. Our previous studies revealed that the transfusion of adult but not neonatal platelets into thrombocytopenic neonatal mice led to an acute increase in monocyte trafficking. We have now found that neonatal but not adult platelets induce monocytes to a myeloid-derived suppressor cell phenotype, typified by increased programmed death ligand 1, that limits T-cell activation in vitro and in vivo. Monocytes previously incubated with neonatal but not adult platelets or platelet releasates limited T-cell activation in vitro. Using an in vivo asthma-like model we also found that the treatment of mice with monocytes before incubation with neonatal platelet releasates limited T-cell activation in a asthma-like model. Platelet-driven effects were dependent on neonatal platelets producing more prostaglandin E2 that signaled through monocyte prostaglandin EP4 receptor. These studies indicate that neonatal platelets have immune-limiting roles in the postnatal period by indirectly limiting T-cell responses, perhaps contributing to the adverse outcomes of platelet transfusions to neonates.