Modulation of indoleamine-2,3-dioxygenase expression and activity by HIV-1 in human macrophages

Benjamin Manéglier*, Benoit Malleret, Gilles J. Guillemin, Odile Spreux-Varoquaux, Philippe Devillier, Christine Rogez-Kreuz, Fabrice Porcheray, Patrice Thérond, Dominique Dormont, Pascal Clayette

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

Human immunodeficiency virus (HIV) infection is often complicated by the development of acquired immunodeficiency syndrome (AIDS) dementia complex (ADC). Implications of kynurenine pathway (KP) are suggested in ADC and other inflammatories brain diseases. The first and regulatory enzyme of the KP is the indoleamine-2,3-dioxygenase (IDO). IDO activation is known to contribute to the modulation of the immune response during various infectious diseases particularly in AIDS. HIV and viral proteins can activate IDO in immune cells leading to an increase catabolism of tryptophan through the KP; the consequence being the production of immuno-modulative and neuroactive metabolites. This mechanism is likely to favour HIV persistence. The present study analysed concomitantly several parameters involved in IDO regulation and activity associated with HIV-1-infection. We investigated relevant intracellular and extracellular mechanisms involved in the regulation of IDO expression and activity during the HIV infection and replication in human monocyte-derived macrophages (MdM). Using a complementary set of in vitro experiments, we found that HIV-1/Ba-L infection induces IDO expression and increases its activity in MdM. We also showed that IDO activation by HIV-1 is likely to be a direct effect of the infection and seems to be independent of IFN-γ production.

Original languageEnglish
Pages (from-to)573-581
Number of pages9
JournalFundamental and Clinical Pharmacology
Volume23
Issue number5
DOIs
Publication statusPublished - Oct 2009
Externally publishedYes

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