How does indoleamine 2,3-dioxygenase contribute to HIV-mediated immune dysregulation.
Infection with the human immunodeficiency virus type 1 (HIV) results in a chronic infection that progressively cripples the host immune defenses. HIV infection is associated with increased tryptophan (trp) catabolism by the cytokine-inducible enzyme indoleamine 2,3-dioxygenase (IDO). IDO has powerful immune suppressive activity, which could contribute to the immune dysfunction observed in HIV-infected patients. In this review we discuss the immune mechanisms that could mediate the HIV-induced increase of IDO activity (such as IFN-gamma, IFN-alpha, CTLA-4/B7 and direct viral exposure). We then consider the current knowledge of IDO-mediated immune suppressive mechanisms with regard to different cell types (CD4(+) T cells, CD8(+) T cells, natural killer cells, B cells and regulatory T cells), from the perspective of their potential consequences for the HIV-infected host. HIV-induced, IDO-mediated trp catabolism may contribute to the perpetuation of HIV infection into its chronic phase by dampening efficient immune anti-viral responses. Therapeutic approaches aimed at manipulating this powerful immune suppressive mechanism might be considered in the setting of HIV infection.
Boasso
Adriano
A
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1360, USA. boassoa@mail.nih.gov
Shearer
Gene M
GM
D000818:Animals; D015658:HIV Infections / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000276:immunology* / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D014364:Tryptophan / Q000172:deficiency / Q000276:immunology
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014364:Tryptophan