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

AROCENA A; ONOFRIO L; PELLEGRINI AV; CARRERA-SILVA AE; PAROLI A; CANO RC; AOKI MP; GEA S

EUROPEAN JOURNAL OF IMMUNOLOGY

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2014 vol. 44 p. 184 - 194

0014-2980

Myeloid-derived suppressor cells (MDSC), CD11b+Gr1+, are key players in the immune suppressive network. During acute infection with Trypanosoma cruzi, the causative agent of Chagas disease, BALB/c mice showed less inflammation and better survival than B6 ones. In this comparative study, we found a higher number of MDSC in spleen and liver of infected BALB/c than in B6 mice.  An analysis of the two major MDSC subsets revealed a greater number of granulocytic cells in spleen and liver from BALB/c respect to B6 mice whereas the monocytic population was the predominant subset in the liver of both strains. Moreover, splenic MDSC purified from infected BALB/c mice inhibited ConA induced splenocyte proliferation. Mechanistic studies demonstrated that reactive oxygen species and nitric oxide were involved in the MDSC suppression activity with a higher number of infected CD8+ T-cells suffering surface-nitration compared to uninfected controls. An up-regulation of NADPH oxidase p47 phox subunit and p-STAT3 occurred in MDSC and infected IL-6KO mice showed less recruitment of MDSC and impaired survival. Remarkably, in vivo depletion of MDSC led to increased production of IL-6, IFNã and the Th17 response with very high parasitemia and mortality. A new facet of MDSC as crucial regulators of inflammation during this infection has been demonstrated.