The Role of L-Tryptophan Kynurenine Pathway Metabolism in Various Infectious Diseases: Focus on Indoleamine 2,3-Dioxygenase 1

The kynurenine (KYN) pathway is the major route of L-tryptophan (L-TRP) catabolism and an anabolic source of nicotinamide-containing nucleotide. To date, three enzymes that catalyze the first and rate-limiting step in the KYN pathway of TRP metabolism have been described: indoleamine 2,3-dioxygenase (IDO) 1, IDO2, and L-tryptophan 2,3-dioxygenase (TDO). In this chapter, we focus on the role of IDO1 in various infectious diseases. IDO1 has a much broader substrate profile for indoleamine-containing compounds and is induced by several proinflammatory cytokines. Substantial increases in the TRP-KYN pathway metabolites occur in human brain, blood, and systemic tissues during immune activation. This enzyme also plays a key role in the immunomodulatory effects on several types of immune cells. Originally known for its regulatory function during pregnancy and chronic inflammation in tumorigenesis, the activity of IDO1 seems to modify the inflammatory state of infectious diseases. Understanding the regulation of IDO1 and the subsequent biochemical reactions is essential for the design of therapeutic strategies in certain immune diseases. Therefore, we will discuss current knowledge about the role of IDO1 and its metabolites during various infectious diseases, e.g., infection by hepatitis virus, HIV, influenza virus, encephalomyocarditis virus, and parasites. Especially the regulation of type I interferon (IFN) production via IDO1 in these infectious diseases is discussed.