Indoleamine 2,3-Dioxygenase Cannot Inhibit Growth in HL-60 Human Neutrophil Granulocytes.

Aims: Neutrophil granulocytes are the major cells involved in ()-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 . Despite its importance, the role of IDO in the intracellular defense against in neutrophils is not well characterized.

Methods: Global gene expression screen was used to evaluate the effect of serovar D infection on the transcriptome of human neutrophil granulocytes. Tryptophan metabolite concentrations in the -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 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 , a known infection- and interferon-induced host gene. The tryptophan-degrading activity of IDO1 was not induced significantly by infection alone, but the addition of IFNG greatly increased its activity. Despite the significant IDO activity in IFNG-treated cells, 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 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.