title: Leishmania major attenuates host immunity by stimulating local indoleamine 2,3-dioxygenase expression.
abstract: Inflammation stimulates immunity but can create immune privilege in some settings. Here, we show that cutaneous Leishmania major infection stimulated expression of the immune regulatory enzyme indoleamine 2,3 dioxygenase (IDO) in local lymph nodes. Induced IDO attenuated the T cell stimulatory functions of dendritic cells and suppressed local T cell responses to exogenous and nominal parasite antigens. IDO ablation reduced local inflammation and parasite burdens, as did pharmacologic inhibition of IDO in mice with established infections. IDO ablation also enhanced local expression of proinflammatory cytokines and induced some CD4(+) T cells to express interleukin (IL) 17. These findings showed that IDO induced by L. major infection attenuated innate and adaptive immune responses. Thus, IDO acts as a molecular switch regulating host responses, and IDO inhibitor drugs are a potential new approach to enhance host immunity to established leishmania infections.
authors.affiliation: Immunotherapy Center, Medical College of Georgia, Augusta, GA 30912, USA.
authors.forename: Levi H C
authors.initials: LH
authors.lastname: Makala
authors.forename: Babak
authors.initials: B
authors.lastname: Baban
authors.forename: Henrique
authors.initials: H
authors.lastname: Lemos
authors.forename: Ahmed R
authors.initials: AR
authors.lastname: El-Awady
authors.forename: Phillip R
authors.initials: PR
authors.lastname: Chandler
authors.forename: De-Yan
authors.initials: DY
authors.lastname: Hou
authors.forename: David H
authors.initials: DH
authors.lastname: Munn
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Mellor
mesh_terms: D000818:Animals; D015496:CD4-Positive T-Lymphocytes; D016207:Cytokines / Q000187:drug effects; D004195:Disease Models, Animal; D006790:Host-Parasite Interactions; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000378:metabolism*; D007378:Interleukins; D018320:Leishmania major / Q000201:enzymology* / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy / Q000469:parasitology*; D008198:Lymph Nodes / Q000201:enzymology / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D013047:Specific Pathogen-Free Organisms; D016176:T-Lymphocyte Subsets
chemical_list: D016207:Cytokines; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007378:Interleukins