Free iron ions decrease indoleamine 2,3-dioxygenase expression and reduce IFNgamma-induced inhibition of Chlamydia trachomatis infection.
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.
Krausse-Opatz
Birgit
B
Department of Rheumatology, Hannover Medical School, Hannover, Germany. birgit.krausse@freenet.de
Wittkop
Ulrike
U
Gutzki
Frank M
FM
Schmidt
Cornelia
C
Jürgens-Saathoff
Barbara
B
Meier
Sabine
S
Beckmann
Bibiana
B
Takikawa
Osamu
O
Morgan
Michael A
MA
Tsikas
Dimitrios
D
Stichtenoth
Dirk O
DO
Wagner
Annette D
AD
Zeidler
Henning
H
Köhler
Lars
L
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
D050503:Indoleamine-Pyrrole 2,3,-Dioxygenase; D007477:Ions; D007371:Interferon-gamma; D014364:Tryptophan