Neonatal granulocytic myeloid-derived suppressor cells possess phagocytic properties during bacterial infection

Abstract Neonates exhibit high susceptibility to bacterial sepsis due to immature immunity in transition from the fetal-maternal environment. Myeloid-derived suppressor cells (MDSCs) are immunosuppressive and more abundant in neonates than at older ages, suggesting a possible role for these cells in susceptibility to infection. MDSCs have been well characterized for their suppression of T cell activity in neonates. Further, although they are related to other myeloid-derived professional phagocytes, their direct response to bacteria during infection has not been rigorously examined. We aimed to thoroughly determine the phagocytic capacity of human MDSCs during bacterial infection. Nearly half of neonatal sepsis deaths in the U.S. are caused by Escherichia coli. Using CD66+ MDSCs isolated from human umbilical cord blood, we compared the ability of MDSCs to phagocytose E. coli to CD14+ monocytes using three approaches: flow cytometry, fluorescence microscopy, and bacterial recovery assays. We found that MDSCs internalize bacteria within acidic compartments in a dose-dependent manner. However, the rate of phagocytosis and killing by MDSCs is significantly reduced compared to monocytes, suggesting that MDSCs are less efficient at microbial uptake and elimination. Overall, we show that granulocytic MDSCs possess the ability to clear bacteria, although with reduced efficiency relative to monocytes. Work is ongoing to further characterize these mechanisms and understand how MDSCs exposed to bacteria interact with other immune cells to control host response during infection. This understanding of MDSC activity during bacterial infection may direct the use of novel therapies to improve neonatal immunity and disease outcome.