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

• Published in: Current drug metabolism Vol. 8; no. 3; p. 217
• Main Authors: Boasso, Adriano, Shearer, Gene M
• Format: Journal Article
• Language: English
• Published: Netherlands 01.04.2007
• Subjects: Animals; HIV Infections - immunology; HIV Infections - metabolism; Humans; Indoleamine-Pyrrole 2,3,-Dioxygenase - immunology; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism; T-Lymphocytes, Regulatory - immunology; Tryptophan - deficiency; Tryptophan - immunology
• ISSN: 1389-2002
• DOI: 10.2174/138920007780362527

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.