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.