title: Opposing biological functions of tryptophan catabolizing enzymes during intracellular infection.
abstract: Recent studies have underscored physiological and pathophysiological roles for the tryptophan-degrading enzyme indolamine 2,3-dioxygenase (IDO) in immune counterregulation. However, IDO was first recognized as an antimicrobial effector, restricting tryptophan availability to Toxoplasma gondii and other pathogens in vitro. The biological relevance of these findings came under question when infectious phenotypes were not forthcoming in IDO-deficient mice. The recent discovery of an IDO homolog, IDO-2, suggested that the issue deserved reexamination. IDO inhibition during murine toxoplasmosis led to 100% mortality, with increased parasite burdens and no evident effects on the immune response. Similar studies revealed a counterregulatory role for IDO during leishmaniasis (restraining effector immune responses and parasite clearance), and no evident role for IDO in herpes simplex virus type 1 (HSV-1) infection. Thus, IDO plays biologically important roles in the host response to diverse intracellular infections, but the dominant nature of this role--antimicrobial or immunoregulatory--is pathogen-specific.
authors: Division of Molecular Immunology, Cincinnati Children's Hospital Research Foundation, and the University of Cincinnati College of Medicine, Ohio, USA.
authors: Senad
authors: S
authors: Divanovic
authors: Nancy M
authors: NM
authors: Sawtell
authors: Aurelien
authors: A
authors: Trompette
authors: Jamie I
authors: JI
authors: Warning
authors: Alexandra
authors: A
authors: Dias
authors: Andrea M
authors: AM
authors: Cooper
authors: George S
authors: GS
authors: Yap
authors: Moshe
authors: M
authors: Arditi
authors: Kenichi
authors: K
authors: Shimada
authors: James B
authors: JB
authors: Duhadaway
authors: George C
authors: GC
authors: Prendergast
authors: Randall J
authors: RJ
authors: Basaraba
authors: Andrew L
authors: AL
authors: Mellor
authors: David H
authors: DH
authors: Munn
authors: Julio
authors: J
authors: Aliberti
authors: Christopher L
authors: CL
authors: Karp
mesh_terms: D000818:Animals; D005260:Female; D006561:Herpes Simplex / Q000201:enzymology* / Q000276:immunology; D018259:Herpesvirus 1, Human; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D016773:Leishmaniasis, Cutaneous / Q000201:enzymology / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014124:Toxoplasmosis, Animal / Q000201:enzymology / Q000276:immunology*; D014364:Tryptophan / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D014364:Tryptophan