title: Myeloid-derived suppressor cells help protective immunity to Leishmania major infection despite suppressed T cell responses.
abstract: Th1/Th2 cytokines play a key role in immune responses to Leishmania major by controlling macrophage activation for NO production and parasite killing. MDSCs, including myeloid precursors and immature monocytes, produce NO and suppress T cell responses in tumor immunity. We hypothesized that NO-producing MDSCs could help immunity to L. major infection. Gr1(hi)(Ly6C(hi)) CD11b(hi) MDSCs elicited by L. major infection suppressed polyclonal and antigen-specific T cell proliferation. Moreover, L. major-induced MDSCs killed intracellular parasites in a NO-dependent manner and reduced parasite burden in vivo. By contrast, treatment with ATRA, which induces MDSCs to differentiate into macrophages, increased development of lesions, parasite load, and T cell proliferation in draining LNs. Altogether, these results indicate that NO-producing MDSCs help protective immunity to L. major infection, despite suppressed T cell proliferation.
authors.affiliation: Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Wânia F
authors.initials: WF
authors.lastname: Pereira
authors.forename: Flávia L
authors.initials: FL
authors.lastname: Ribeiro-Gomes
authors.forename: Landi V Costilla
authors.initials: LV
authors.lastname: Guillermo
authors.forename: Natália S
authors.initials: NS
authors.lastname: Vellozo
authors.forename: Fabrício
authors.initials: F
authors.lastname: Montalvão
authors.forename: George A
authors.initials: GA
authors.lastname: Dosreis
authors.forename: Marcela F
authors.initials: MF
authors.lastname: Lopes
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D060467:Disease Resistance / Q000276:immunology; D007111:Immunity, Cellular; D007165:Immunosuppression Therapy; D018320:Leishmania major / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009000:Monocytes / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D022423:Myeloid Cells / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology; D013234:Stem Cells / Q000276:immunology* / Q000469:parasitology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000469:parasitology