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

Abstract

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.

Diagnostic accuracy of plasma kynurenine/tryptophan ratio, measured by enzyme-linked immunosorbent assay, for pulmonary tuberculosis

“…Furthermore, HIV-infected patients have a higher plasma K/T ratio than HIV-uninfected individuals. The size of the HIV viral reservoir impacts the plasma K/T ratio (Chen et al, 2019;Adu-Gyamfi et al, 2019). Broad evidence indicates that the K/ T ratio is mildly increased in HIV infection and highly increased in active TB (Suchard et al, 2020;Adu-Gyamfi et al, 2019).…”

IDO Expression in Cancer: Different Compartment, Different Functionality?

“…A role for IDO in the IFNγ-mediated differentiation of monocytes into M2-type macrophages has also been proposed ( 72 , 73 ). M2-macrophages are associated with tumor progression in prostate, colon, breast cancer, gastric and ovarian cancer ( 137 – 144 ). In vitro stimulation of monocytes with IFNγ increased the M2/M1 ratio, while silencing of IDO in monocytes resulted in upregulation of pro-inflammatory M1-macrophages ( 74 ).…”

An Insight into the Roles of Dietary Tryptophan and Its Metabolites in Intestinal Inflammation and Inflammatory Bowel Disease

“…[28] Owing to these essential roles of Trp, some recent reviews have been done on the Trp metabolism, particularly through the KYN pathway that prevents inflammation and induces long-term immune tolerance. [14,29] However, very little attention has been paid to the Trp metabolism through the indole and 5-HT pathways in regulating inflammation. In particular, the specific mechanisms and interrelationships among the three metabolic pathways of Trp in the perspective of regulating inflammation are yet to be elucidated.…”