Related Experiment Video
Updated: Oct 12, 2025
A Human Fallopian Tube Model for Investigation of C. trachomatis Infections
Published on: August 11, 2012
Indoleamine 2,3-Dioxygenase Cannot Inhibit Chlamydia trachomatis Growth in HL-60 Human Neutrophil Granulocytes
Dezső P Virok1, Ferenc Tömösi2, Anikó Keller-Pintér3
1Department of Medical Microbiology, Albert Szent-Györgyi Health Center and Faculty of Medicine, University of Szeged, Szeged, Hungary.
Insights
Indoleamine 2,3-dioxygenase (IDO) activity in neutrophils does not inhibit Chlamydia trachomatis growth, even when induced by interferon-gamma. Further research is needed to understand this lack of inhibition in neutrophils compared to other cell types.
Area of Science:
- Immunology
- Microbiology
- Molecular Biology
Background:
- Neutrophils are key in Chlamydia trachomatis-mediated inflammation.
- Indoleamine 2,3-dioxygenase (IDO) is crucial for antichlamydial defense by degrading tryptophan.
- The role of IDO in neutrophil defense against Chlamydia is not well understood.
Purpose of the Study:
- To investigate the effect of Chlamydia trachomatis infection on neutrophil gene expression.
- To determine the role of IDO in the intracellular defense against Chlamydia in human neutrophils.
Main Methods:
- Global gene expression screening of human neutrophils infected with C. trachomatis.
- Measurement of tryptophan metabolite concentrations using UHPLC-MS/MS in infected and/or IFNG-treated neutrophils.
Main Results:
- C. trachomatis infection significantly altered neutrophil gene expression, upregulating 1,295 and repressing 1,510 genes.
- IDO1 was upregulated, but its tryptophan-degrading activity was not significantly induced by C. trachomatis alone; IFNG greatly increased IDO1 activity.
- Despite significant IDO activity in IFNG-treated neutrophils, C. trachomatis growth was not inhibited, contrasting with findings in epithelial cells.
Conclusions:
- IDO activity does not inhibit C. trachomatis growth in human neutrophils.
- Further investigation is required to determine if IDO activity was insufficient or if other growth-promoting mechanisms are involved in neutrophils.
Aims:
Neutrophil granulocytes are the major cells involved in Chlamydia trachomatis (C. trachomatis)-mediated inflammation and histopathology. A key protein in human intracellular antichlamydial defense is the tryptophan-degrading enzyme indoleamine 2,3-dioxygenase (IDO) which limits the growth of the tryptophan auxotroph Chlamydia. Despite its importance, the role of IDO in the intracellular defense against Chlamydia in neutrophils is not well characterized.
Methods:
Global gene expression screen was used to evaluate the effect of C. trachomatis serovar D infection on the transcriptome of human neutrophil granulocytes. Tryptophan metabolite concentrations in the Chlamydia-infected and/or interferon-gamma (IFNG)-treated neutrophils were measured by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS).
Results:
Our results indicate that the C. trachomatis infection had a major impact on neutrophil gene expression, inducing 1,295 genes and repressing 1,510 genes. A bioinformatics analysis revealed that important factors involved in the induction of neutrophil gene expression were the interferon-related transcription factors such as IRF1-5, IRF7-9, STAT2, ICSB, and ISGF3. One of the upregulated genes was ido1, a known infection- and interferon-induced host gene. The tryptophan-degrading activity of IDO1 was not induced significantly by Chlamydia infection alone, but the addition of IFNG greatly increased its activity. Despite the significant IDO activity in IFNG-treated cells, C. trachomatis growth was not affected by IFNG. This result was in contrast to what we observed in HeLa human cervical epithelial cells, where the IFNG-mediated inhibition of C. trachomatis growth was significant and the IFNG-induced IDO activity correlated with growth inhibition.
Conclusions:
IDO activity was not able to inhibit chlamydial growth in human neutrophils. Whether the IDO activity was not high enough for inhibition or other chlamydial growth-promoting host mechanisms were induced in the infected and interferon-treated neutrophils needs to be further investigated.
