Role of indoleamine 2,3-dioxygenase in antimicrobial defence and immuno-regulation: tryptophan depletion versus production of toxic kynurenines.

Tryptophan metabolism occurs via the protohemoprotein enzymes tryptophan 2,3-dioxygenase (TDO) and indoleamine 2,3-dioxygenase (IDO), the latter action of which has a number of effects in the body including both antimicrobial defence and immune regulation. Whilst the antimicrobial action of IDO is largely due to depletion of the essential amino acid tryptophan, the immune regulatory function of IDO is still unclear and controversial. The list of pathogens that are "sensitive" to IDO-mediated tryptophan degradation covers intra-cellular parasites such as toxoplasma and possibly plasmodia, viruses (herpes viruses) to intra-cellular bacteria (chlamydia and rickettsia) and extra-cellular bacteria such as streptococci, enterococci and staphylococci. Immune regulation may be a consequence of tryptophan depletion, the accumulation of immune-active or toxic metabolites or due to other signalling events. This review covers the latest data and controversy pertaining to the antimicrobial and immune regulatory effects of tryptophan metabolism.