Myeloid-derived suppressor cells are key players in the resolution of inflammation during a model of acute infection

Abstract

Myeloid-derived suppressor cells (MDSCs) are key players in the immune suppressivenetwork. During acute infection with the causative agent of Chagas disease,Trypanosomacruzi, BALB/c mice show less inflammation and better survival than C57BL/6 (B6) mice.In this comparative study, we found a higher number of MDSCs in the spleens and liversof infected BALB/c mice compared with infected B6 mice. An analysis of the two majorMDSCs subsets revealed a greater number of granulocytic cells in the spleens and liversof BALB/c mice when compared with that in B6 mice. Moreover, splenic MDSCs purifiedfrom infected BALB/c mice inhibited ConA-induced splenocyte proliferation. Mechanisticstudies demonstrated that ROS and nitric oxide were involved in the suppressive activityof MDSCs, with a higher number of infected CD8+T cells suffering surface-nitrationcompared to uninfected controls. An upregulation of NADPH oxidase p47 phox subunitand p-STAT3 occurred in MDSCs and infected IL-6 KO mice showed less recruitment ofMDSCs and impaired survival. Remarkably, in vivo depletion of MDSCs led to increasedproduction of IL-6, IFN-γ, and a Th17 response with very high parasitemia and mortality.These findings demonstrate a new facet of MDSCs as crucial regulators of inflammationduringT. cruziinfection.