title: Free iron ions decrease indoleamine 2,3-dioxygenase expression and reduce IFNgamma-induced inhibition of Chlamydia trachomatis infection.
abstract: Interferon-gamma (IFNgamma)-mediated indoleamine 2,3-dioxygenase (IDO) expression, important in innate immunity, immune suppression, and tolerance, can be counteracted by ferrous iron (FeSO(4)). Elevation of intracellular iron levels during stimulation with IFNgamma impeded IFNgamma-induced IDO mRNA and protein expression in HEp-2 cells. Decreased IDO expression was accompanied by decreased tryptophan degradation. Accordingly, IFNgamma-mediated suppressing effects on Chlamydia trachomatis (CT) infection were reduced or even abolished in the presence of FeSO(4). Conversely, lowering intracellular iron levels by deferoxamine (DFO) did not increase IFNgamma-induced IDO expression but potentiated Chlamydia-suppressing effects by lowering intracellular iron availability. Additionally, DFO led to a CT-induced IDO expression in HEp-2 cells not treated with IFNgamma. In summary, this study demonstrates that iron acts as a regulatory element for modulating IDO expression, in addition to its function as an essential element for chlamydial growth. This may represent an important control mechanism of IDO expression at the transcriptional level.
authors.affiliation: Department of Rheumatology, Hannover Medical School, Hannover, Germany. birgit.krausse@freenet.de
authors.forename: Birgit
authors.initials: B
authors.lastname: Krausse-Opatz
authors.forename: Ulrike
authors.initials: U
authors.lastname: Wittkop
authors.forename: Frank M
authors.initials: FM
authors.lastname: Gutzki
authors.forename: Cornelia
authors.initials: C
authors.lastname: Schmidt
authors.forename: Barbara
authors.initials: B
authors.lastname: Jürgens-Saathoff
authors.forename: Sabine
authors.initials: S
authors.lastname: Meier
authors.forename: Bibiana
authors.initials: B
authors.lastname: Beckmann
authors.forename: Osamu
authors.initials: O
authors.lastname: Takikawa
authors.forename: Michael A
authors.initials: MA
authors.lastname: Morgan
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Tsikas
authors.forename: Dirk O
authors.initials: DO
authors.lastname: Stichtenoth
authors.forename: Annette D
authors.initials: AD
authors.lastname: Wagner
authors.forename: Henning
authors.initials: H
authors.lastname: Zeidler
authors.forename: Lars
authors.initials: L
authors.lastname: Köhler
mesh_terms: D002460:Cell Line; D002690:Chlamydia Infections / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002692:Chlamydia trachomatis / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase / Q000235:genetics* / Q000378:metabolism; D007371:Interferon-gamma / Q000235:genetics / Q000276:immunology*; D007477:Ions / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism
chemical_list: D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007477:Ions; D007371:Interferon-gamma; D014364:Tryptophan