A Schistosoma japonicum Infection Promotes the Expansion of Myeloid-Derived Suppressor Cells by Activating the JAK/STAT3 Pathway

Myeloid-derived suppressor cells (MDSCs), a heterogeneous group of immune cells from the myeloid lineage, play an important part in suppression of host immune responses during many pathologic conditions, including cancer and infectious diseases. Thus, understanding the functional diversity of these cells as well as the underlying mechanisms is crucial for the development of disease control strategies. The role of MDSCs during Schistosoma japonicum infection, however, is not clear, and there is a lack of systematic study so far. In this study, we provide strong evidence that the soluble egg Ag (SEA) and schistosome worm Ag (SWA) of S. japonicum enhance the accumulation of MDSCs. Ag-induced MDSCs have more potent suppressive effects on T cell responses than do control MDSCs in both in vivo S. japonicum infection and in vitro SEA- and SWA-treated mouse bone marrow cells experiments. Interestingly, the enhanced suppressive activity of MDSCs by Ag administration was coupled with a dramatic induction of the NADPH oxidase subunits gp91 phox and p47 phox and was dependent on the production of reactive oxygen species. Moreover, mechanistic studies revealed that the Ag effects are mediated by JAK/STAT3 signaling. Inhibition of STAT3 phosphorylation by the JAK inhibitor JSI-124 almost completely abolished the Ag effects on the MDSCs. In summary, this study sheds new light on the immune modulatory role of SEA and SWA and demonstrates that the expansion of MDSCs may be an important element of a cellular network regulating immune responses during S. japonicum infection.