{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T21:49:40Z","timestamp":1781214580770,"version":"3.54.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T00:00:00Z","timestamp":1636329600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Aims<\/jats:title><jats:p>Neutrophil granulocytes are the major cells involved in <jats:italic>Chlamydia trachomatis<\/jats:italic> (<jats:italic>C. trachomatis<\/jats: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 <jats:italic>Chlamydia<\/jats:italic>. Despite its importance, the role of IDO in the intracellular defense against <jats:italic>Chlamydia<\/jats:italic> in neutrophils is not well characterized.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Global gene expression screen was used to evaluate the effect of <jats:italic>C. trachomatis<\/jats:italic> serovar D infection on the transcriptome of human neutrophil granulocytes. Tryptophan metabolite concentrations in the <jats:italic>Chlamydia<\/jats:italic>-infected and\/or interferon-gamma (IFNG)-treated neutrophils were measured by ultra-high-performance liquid chromatography\u2013tandem mass spectrometry (UHPLC\u2013MS\/MS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our results indicate that the <jats:italic>C. trachomatis<\/jats: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 <jats:italic>ido1<\/jats:italic>, a known infection- and interferon-induced host gene. The tryptophan-degrading activity of IDO1 was not induced significantly by <jats:italic>Chlamydia<\/jats:italic> infection alone, but the addition of IFNG greatly increased its activity. Despite the significant IDO activity in IFNG-treated cells, <jats:italic>C. trachomatis<\/jats: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 <jats:italic>C. trachomatis<\/jats:italic> growth was significant and the IFNG-induced IDO activity correlated with growth inhibition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats: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.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2021.717311","type":"journal-article","created":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T07:09:59Z","timestamp":1636355399000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Indoleamine 2,3-Dioxygenase Cannot Inhibit Chlamydia trachomatis Growth in HL-60 Human Neutrophil Granulocytes"],"prefix":"10.3389","volume":"12","author":[{"given":"Dezs\u0151 P.","family":"Virok","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ferenc","family":"T\u00f6m\u00f6si","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anik\u00f3","family":"Keller-Pint\u00e9r","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kitti","family":"Szab\u00f3","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anita","family":"Bogdanov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szil\u00e1rd","family":"Poliska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsolt","family":"R\u00e1zga","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bella","family":"Bruszel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Cseh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00e1vid","family":"K\u00f3kai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D\u00f3ra","family":"Par\u00f3czai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9ria","family":"Endr\u00e9sz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"Jan\u00e1ky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katalin","family":"Buri\u00e1n","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,11,8]]},"reference":[{"key":"B1","unstructured":"Chlamydia\n            MohseniM\n            SungS\n            TakovV\n          Treasure Island (FLStatPearls PublishingStatPearls"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.68.5.2870-2879.2000","article-title":"In Situ Analysis of the Evolution of the Primary Immune Response in Murine Chlamydia Trachomatis Genital Tract Infection","volume":"68","author":"Morrison","year":"2000","journal-title":"Infect Immun"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2008.00639.x","article-title":"A Distinct Cellular Profile Is Seen in the Human Endocervix During Chlamydia Trachomatis Infection","volume":"60","author":"Ficarra","year":"2008","journal-title":"Am J Reprod Immunol N Y N 1989"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.00844-10","article-title":"Human Conjunctival Transcriptome Analysis Reveals the Prominence of Innate Defense in Chlamydia Trachomatis Infection","volume":"78","author":"Natividad","year":"2010","journal-title":"Infect Immun"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1155\/2019\/8604958","article-title":"Chlamydia and Its Many Ways of Escaping the Host Immune System","volume":"2019","author":"Wong","year":"2019","journal-title":"J Pathog"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1711356115","article-title":"Pathology After Chlamydia Trachomatis Infection Is Driven by Nonprotective Immune Cells That Are Distinct From Protective Populations","volume":"115","author":"Lijek","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.62.9.3705-3711.1994","article-title":"Tryptophan Depletion as a Mechanism of Gamma Interferon-Mediated Chlamydial Persistence","volume":"62","author":"Beatty","year":"1994","journal-title":"Infect Immun"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.74.1.225-238.2006","article-title":"Comparison of Gamma Interferon-Mediated Antichlamydial Defense Mechanisms in Human and Mouse Cells","volume":"74","author":"Roshick","year":"2006","journal-title":"Infect Immun"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2019.00192","article-title":"Indoleamine 2,3-Dioxygenase Activity in Chlamydia Muridarum and Chlamydia Pneumoniae Infected Mouse Lung Tissues","volume":"9","author":"Virok","year":"2019","journal-title":"Front Cell Infect Microbiol"},{"key":"B10","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/s1369-5274(02)00291-6","article-title":"T Cell Responses to Chlamydia Trachomatis","volume":"5","author":"Loomis","year":"2002","journal-title":"Curr Opin Microbiol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.66.12.5867-5875.1998","article-title":"Role of NK Cells in Early Host Response to Chlamydial Genital Infection","volume":"66","author":"Tseng","year":"1998","journal-title":"Infect Immun"},{"key":"B12","unstructured":"Cell Type Atlas Ido1"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.31.3.1161-1176.1981","article-title":"Purification and Partial Characterization of the Major Outer Membrane Protein of Chlamydia Trachomatis","volume":"31","author":"Caldwell","year":"1981","journal-title":"Infect Immun"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-60761-404-3_9","article-title":"Manipulation of Neutrophil-Like HL-60 Cells for the Study of Directed Cell Migration","volume":"591","author":"Millius","year":"2010","journal-title":"Methods Mol Biol Clifton NJ"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-8-426","article-title":"DAVID Knowledgebase: A Gene-Centered Database Integrating Heterogeneous Gene Annotation Resources to Facilitate High-Throughput Gene Functional Analysis","volume":"8","author":"Sherman","year":"2007","journal-title":"BMC Bioinf"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz369","article-title":"G:Profiler: A Web Server for Functional Enrichment Analysis and Conversions of Gene Lists (2019 Update)","volume":"47","author":"Raudvere","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2020.113246","article-title":"A Validated UHPLC-MS Method for Tryptophan Metabolites: Application in the Diagnosis of Multiple Sclerosis","volume":"185","author":"T\u00f6m\u00f6si","year":"2020","journal-title":"J Pharm BioMed Anal"},{"key":"B18","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1186\/s10194-021-01239-1","article-title":"Clinical Relevance of Depressed Kynurenine Pathway in Episodic Migraine Patients: Potential Prognostic Markers in the Peripheral Plasma During the Interictal Period","volume":"22","author":"Tuka","year":"2021","journal-title":"J Headache Pain"},{"key":"B19","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","article-title":"Rapid Colorimetric Assay for Cellular Growth and Survival: Application to Proliferation and Cytotoxicity Assays","volume":"65","author":"Mosmann","year":"1983","journal-title":"J Immunol Methods"},{"key":"B20","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.mimet.2015.11.010","article-title":"High Dynamic Range Detection of Chlamydia Trachomatis Growth by Direct Quantitative PCR of the Infected Cells","volume":"120","author":"Eszik","year":"2016","journal-title":"J Microbiol Methods"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.jim.2010.01.004","article-title":"TB Trials Study Group. Comparison of Different Standards for Real-Time PCR-Based Absolute Quantification","volume":"354","author":"Dhanasekaran","year":"2010","journal-title":"J Immunol Methods"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.05659-11","article-title":"Inhibition of Indoleamine 2,3-Dioxygenase Activity by Levo-1-Methyl Tryptophan Blocks Gamma Interferon-Induced Chlamydia Trachomatis Persistence in Human Epithelial Cells","volume":"79","author":"Ibana","year":"2011","journal-title":"Infect Immun"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2006.05465.x","article-title":"Global Transcriptional Upregulation in the Absence of Increased Translation in Chlamydia During IFNgamma-Mediated Host Cell Tryptophan Starvation","volume":"62","author":"Ouellette","year":"2006","journal-title":"Mol Microbiol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.172.3.1768","article-title":"Chlamydia Pneumoniae Multiply in Neutrophil Granulocytes and Delay Their Spontaneous Apoptosis","volume":"172","author":"van Zandbergen","year":"2004","journal-title":"J Immunol Baltim Md 1950"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1128\/IAI.67.4.1666-1671.1999","article-title":"Intracellular Tryptophan Pool Sizes may Account for Differences in Gamma Interferon-Mediated Inhibition and Persistence of Chlamydial Growth in Polarized and Nonpolarized Cells","volume":"67","author":"Kane","year":"1999","journal-title":"Infect Immun"},{"key":"B26","unstructured":"Peprotech Recombinant Human IFNG Data Sheet"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1128\/iai.53.2.347-351.1986","article-title":"Induction of Tryptophan Catabolism Is the Mechanism for Gamma-Interferon-Mediated Inhibition of Intracellular Chlamydia Psittaci Replication in T24 Cells","volume":"53","author":"Byrne","year":"1986","journal-title":"Infect Immun"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2016.00605","article-title":"Distinct Patterns of Tryptophan Maintenance in Tissues During Kynurenine Pathway Activation in Simian Immunodeficiency Virus-Infected Macaques","volume":"7","author":"Drewes","year":"2016","journal-title":"Front Immunol"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.32.41","article-title":"Anti-Infectious Activity of Tryptophan Metabolites in the L-Tryptophan-L-Kynurenine Pathway","volume":"32","author":"Narui","year":"2009","journal-title":"Biol Pharm Bull"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/s1734-1140(11)70522-9","article-title":"Effect of Kynurenic Acid on the Viability of Probiotics In Vitro","volume":"63","author":"Dolecka","year":"2011","journal-title":"Pharmacol Rep PR"},{"key":"B31","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1007\/s002239900485","article-title":"Up-Regulation of Inducible Nitric Oxide (NO) Synthase and NO Production in HL-60 Cells Stimulated to Differentiate by Phorbol 12-Myristate 13-Acetate Plus 1,25-Dihydroxyvitamin D3 Is Not Obtained With Dimethylsulfoxide Plus 1,25-Dihydroxyvitamin D3","volume":"63","author":"Kawase","year":"1998","journal-title":"Calcif Tissue Int"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)36645-0","article-title":"Nitric Oxide Inhibits Indoleamine 2,3-Dioxygenase Activity in Interferon-Gamma Primed Mononuclear Phagocytes","volume":"269","author":"Thomas","year":"1994","journal-title":"J Biol Chem"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.717311\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,8]],"date-time":"2021-11-08T07:10:04Z","timestamp":1636355404000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2021.717311\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,8]]},"references-count":32,"alternative-id":["10.3389\/fimmu.2021.717311"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2021.717311","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,11,8]]},"article-number":"717311"}}