Neonatal granulocytic MDSCs possess phagocytic properties during bacterial infection.

Abstract

Myeloid-derived suppressor cells (MDSCs) are an immunosuppressive cell type found in high abundance in early life. Currently, there has been limited mechanistic understanding of MDSC phagocytosis of bacteria and the corresponding consequences in the context of acute infection. We set out to determine whether human granulocytic MDSCs have phagocytic capacity that is comparable to other professional phagocytes. To investigate these properties, we utilized fluorescent confocal microscopy, flow cytometry, and bacterial burden assays. We demonstrate that human granulocytic MDSCs phagocytose E. coli O1:K1:H7, and subsequently traffic the bacteria into acidic compartments similar to other phagocytes. However, MDSCs were significantly less efficient at bacterial uptake and killing compared to monocytes. This activity is associated with an inflammatory response, but the amount of TNF gene and protein expression was reduced in infected MDSCs compared to monocytes. Interestingly, we also found that MDSCs release DNA (MeDNA) into the extracellular space that resembles neutrophil extracellular traps. We found that MeDNA had some impact on bacterial viability in single cultures, with an increase in bacterial recovery in MDSCs treated with DNAse. However, MeDNA did not impact the ability of monocytes to eliminate bacteria in co-cultures, suggesting that MDSC extracellular DNA does not compromise monocyte function. Overall, our data reveals mechanistic insight into MDSC activity during infection that includes the kinetics and efficiency of bacterial uptake, elimination through trafficking to acidified compartments, and inflammatory contributions relative to primary human monocytes. These results enhance our understanding of MDSC contributions during acute bacterial infection and identify host-directed targets for immune intervention to improve outcomes and reduce susceptibility to infection early in life.