Interferon‐γ‐Induced Activation of Indoleamine 2,3‐Dioxygenase in Cord Blood Monocyte‐Derived Macrophages Inhibits the Growth of Group B Streptococci

Abstract

Neonatal sepsis is most often caused by group B streptococci (GBS) and is a major cause of death in the neonatal period. The response of the immune system in the newborn child has received much attention and is thought to be deficient in a number of ways. The effector response of neonatal monocyte-derived macrophages (MDM) was investigated. Interferon-gamma induced the activation of indoleamine 2,3-dioxygenase in MDM and inhibited the growth of GBS. Both effects were enhanced by the addition of tumor necrosis factor-alpha to the culture conditions. The coincident supplementation of L-tryptophan with the bacteria abrogated the bacterial growth inhibition, thus confirming the causative role of L-tryptophan depletion. Control of the extracellular as well as intracellular L-tryptophan levels may thus be one of the effector mechanisms with which the immune system defends the host against GBS dissemination and disease.

Differential effects of the tryptophan metabolite3‐hydroxyanthranilic acid on the proliferation of human CD8+ T cells induced by TCR triggering or homeostatic cytokines

“…IDO activity has first been described as being induced by IFN treatment of monocytes, macrophages and other types of cells potentially endowed with phagocytic and antigen-presenting capacity [15][16][17]. In this context, it was hypothesized that IDO production by either depleting tryptophan or by the production of toxic metabolites would help hampering bacterial proliferation, ultimately boosting host's defenses [18].…”

Indoleamine 2,3-Dioxygenase Expression in Transplanted NOD Islets Prolongs Graft Survival After Adoptive Transfer of Diabetogenic Splenocytes

“…Interestingly, nicotinamide has been shown to protect ␤-cells from certain toxins and the effects of nitric oxide (31). There is evidence for a role of tryptophan catabolism, by the induction of the specific enzyme IDO, in the immune response of neuronal inflammation due to disease or injury, as well as its involvement in malignancy (9,10), in vitro antimicrobial activity (11)(12)(13)(14), and in vitro inhibition of T-cell proliferation (8). More recently, tryptophan depletion has been linked to the maintenance of pregnancy (18).…”

“…Localized depletion of tryptophan in vivo has also been implicated in the immune evasion of certain tumors (9,10). Indoleamine 2,3-dioxygenase (IDO), the enzyme that regulates the rate-limiting step involved in the catabolism of tryptophan to kyneurenine, is also involved in the control of microbial infections (11)(12)(13)(14) and has been shown to have antioxidant properties (15)(16)(17). Pregnancy maintenance has also been associated with tryptophan catabolism by preventing the proliferation of maternal T-cells in response to tissues of the fetus expressing HLA alleles of the father (18).…”

3-Hydroxyanthranilic acid inhibits PDK1 activation and suppresses experimental asthma by inducing T cell apoptosis

“…Previous reports demonstrated that the depletion of trp by IDO in the intracellular pool or microenvironment mediated an antimicrobial activity (11). Similar logic was applied to explain the immunomodulatory effects induced by IDO (4,5,12,13).…”