IMEX   05356
INSTITUTO DE MEDICINA EXPERIMENTAL
Unidad Ejecutora - UE
artículos
Título:
Myeloid-derived suppressor cells are key players in the resolution of inflammation during a model of acute infection
Autor/es:
AROCENA AR, ONOFRIO LI, PELLEGRINI AV, CARRERA SILVA AE, PAROLI A, CANO RC, AOKI MP, GEA S.
Revista:
EUROPEAN JOURNAL OF IMMUNOLOGY
Editorial:
WILEY-V C H VERLAG GMBH
Referencias:
Lugar: Weinheim; Año: 2014 vol. 44 p. 184 - 194
ISSN:
0014-2980
Resumen:
Myeloid-derived suppressor cells (MDSCs) are key players in the immunesuppressive network. During acute infection with the causative agent of Chagasdisease, Trypanosoma cruzi, BALB/c mice show less inflammation and bettersurvival than C57BL/6 (B6) mice. In this comparative study, we found a highernumber of MDSCs in the spleens and livers of infected BALB/c mice compared withinfected B6 mice. An analysis of the two major MDSCs subsets revealed a greaternumber of granulocytic cells in the spleens and livers of BALB/c mice whencompared with that in B6 mice. Moreover, splenic MDSCs purified from infectedBALB/c mice inhibited ConA-induced splenocyte proliferation. Mechanistic studies demonstrated that ROS and nitric oxide were involved in the suppressive activity of MDSCs, with a higher number of infected CD8(+) T cells sufferingsurface-nitration compared to uninfected controls. An upregulation of NADPHoxidase p47 phox subunit and p-STAT3 occurred in MDSCs and infected IL-6 KO mice showed less recruitment of MDSCs and impaired survival. Remarkably, in vivodepletion of MDSCs led to increased production of IL-6, IFN-γ, and a Th17response with very high parasitemia and mortality. These findings demonstrate anew facet of MDSCs as crucial regulators of inflammation during T. cruziinfection.