title: 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 suppressive network. During acute infection with the causative agent of Chagas disease, Trypanosoma cruzi, 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 livers of infected BALB/c mice compared with infected B6 mice. An analysis of the two major MDSCs subsets revealed a greater number of granulocytic cells in the spleens and livers of BALB/c mice when compared with that in B6 mice. Moreover, splenic MDSCs purified from infected BALB/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 suffering surface-nitration compared to uninfected controls. An upregulation of NADPH oxidase 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 vivo depletion of MDSCs led to increased production 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 inflammation during T. cruzi infection.
authors.affiliation: Centro de Investigación en Bioquímica Clínica e Inmunología, CIBICI-CONICET, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba, Cordoba, Argentina.
authors.forename: Alfredo R
authors.initials: AR
authors.lastname: Arocena
authors.forename: Luisina I
authors.initials: LI
authors.lastname: Onofrio
authors.forename: Andrea V
authors.initials: AV
authors.lastname: Pellegrini
authors.forename: Antonio E
authors.initials: AE
authors.lastname: Carrera Silva
authors.forename: Augusto
authors.initials: A
authors.lastname: Paroli
authors.forename: Roxana C
authors.initials: RC
authors.lastname: Cano
authors.forename: Maria P
authors.initials: MP
authors.lastname: Aoki
authors.forename: Susana
authors.initials: S
authors.lastname: Gea
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D014355:Chagas Disease / Q000276:immunology*; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D006098:Granulocytes / Q000276:immunology*; D006801:Humans; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D022423:Myeloid Cells / Q000276:immunology*; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology*; D014349:Trypanosoma cruzi / Q000276:immunology*
chemical_list: D016207:Cytokines; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; D019255:NADPH Oxidases; C060505:neutrophil cytosolic factor 1
keywords: Inflammation; MDSCs; Nitric oxide; ROS; Trypanosoma cruzi