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.