How does indoleamine 2, 3-dioxygenase contribute to HIV-mediated immune dysregulation

A Boasso, GM Shearer - Current drug metabolism, 2007 - ingentaconnect.com
A Boasso, GM Shearer
Current drug metabolism, 2007ingentaconnect.com
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 …
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-γ , IFN-α , 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.
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