Indoleamine 2, 3-Dioxygenase-Mediated Tryptophan Catabolism: A Leading Star or Supporting Act in the Tuberculosis and HIV Pas-de-Deux?

• Published in: Frontiers in cellular and infection microbiology Vol. 9; p. 372
• Main Authors: Adu-Gyamfi, Clement Gascua, Savulescu, Dana, George, Jaya Anna, Suchard, Melinda Shelley
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 29.10.2019
• Subjects: active TB; Cellular and Infection Microbiology; IDO; kynurenine/tryptophan ratio; latent TB; nicotinamide; latent TB; IDO; kynurenine/tryptophan ratio; active TB; nicotinamide
• ISSN: 2235-2988; 2235-2988
• DOI: 10.3389/fcimb.2019.00372

Progression from latency to active Tuberculosis (TB) disease is mediated by incompletely understood host immune factors. The definitive characteristic of progressive human immunodeficiency virus (HIV) disease is a severe loss in number and function of T lymphocytes. Among the many possible mediators of T lymphocyte loss and ineffective function is the activity of the immune-modulatory enzyme indoleamine 2,3-dioxygenase (IDO). IDO is the rate-limiting enzyme converting tryptophan to kynurenine. IDO activity was initially recognized to mediate tolerance at the foeto-maternal interface. Recently, IDO activity has also been noted to play a critical role in immune tolerance to pathogens. Studies of host immune and metabolic mediators have found IDO activity significantly elevated in HIV and TB disease. In this review, we explore the link between IDO-mediated tryptophan catabolism and the presence of active TB disease in HIV-infected patients. We draw attention to increased IDO activity as a key factor marking the progression from latent to active TB disease in HIV-infected patients.