AUTHOR=Virok Dezső P. , Tömösi Ferenc , Keller-Pintér Anikó , Szabó Kitti , Bogdanov Anita , Poliska Szilárd , Rázga Zsolt , Bruszel Bella , Cseh Zsuzsanna , Kókai Dávid , Paróczai Dóra , Endrész Valéria , Janáky Tamás , Burián Katalin 

TITLE=Indoleamine 2,3-Dioxygenase Cannot Inhibit Chlamydia trachomatis Growth in HL-60 Human Neutrophil Granulocytes

JOURNAL=Frontiers in Immunology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2021.717311

DOI=10.3389/fimmu.2021.717311

ISSN=1664-3224

ABSTRACT=<sec><title>Aims</title><p>Neutrophil granulocytes are the major cells involved in <italic>Chlamydia trachomatis</italic> (<italic>C. trachomatis</italic>)-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 <italic>Chlamydia</italic>. Despite its importance, the role of IDO in the intracellular defense against <italic>Chlamydia</italic> in neutrophils is not well characterized.</p></sec><sec><title>Methods</title><p>Global gene expression screen was used to evaluate the effect of <italic>C. trachomatis</italic> serovar D infection on the transcriptome of human neutrophil granulocytes. Tryptophan metabolite concentrations in the <italic>Chlamydia</italic>-infected and/or interferon-gamma (IFNG)-treated neutrophils were measured by ultra-high-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS).</p></sec><sec><title>Results</title><p>Our results indicate that the <italic>C. trachomatis</italic> 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 <italic>ido1</italic>, a known infection- and interferon-induced host gene. The tryptophan-degrading activity of IDO1 was not induced significantly by <italic>Chlamydia</italic> infection alone, but the addition of IFNG greatly increased its activity. Despite the significant IDO activity in IFNG-treated cells, <italic>C. trachomatis</italic> 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 <italic>C. trachomatis</italic> growth was significant and the IFNG-induced IDO activity correlated with growth inhibition.</p></sec><sec><title>Conclusions</title><p>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.</p></sec>