Myeloid-derived suppressor cells help protective immunity to Leishmania major infection despite suppressed T cell responses

Journal of Leukocyte Biology

Wânia F. Pereira¹  Landi V. Costilla Guillermo¹  George A. DosReis,  and²  NatÃlia S. Vellozo¹  Marcela F. Lopes¹  FlÃvia L. Ribeiro-Gomes¹  Fabrício Montalvão¹ 

[1] Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil;;Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil; and  Instituto Nacional para Pesquisa Translacional em Saúde e Ambiente na Região Amazônica, Conselho Nacional de Desenvolvimento Científico e Tecnológico/MCT, Brazil

关键词: ATRA;    MDSCs;    monocytes;    nitric oxide;    parasites;    suppression;   

DOI  :  10.1189/jlb.1110608

学科分类：生理学

来源: Federation of American Societies for Experimental Biology

【 摘 要 】

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. Gr1hi(Ly6Chi) CD11bhi 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.

【 授权许可】

Unknown