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

AimsNeutrophil 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...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Dezső P. Virok, Ferenc Tömösi, Anikó Keller-Pintér, Kitti Szabó, Anita Bogdanov, Szilárd Poliska, Zsolt Rázga, Bella Bruszel, Zsuzsanna Cseh, Dávid Kókai, Dóra Paróczai, Valéria Endrész, Tamás Janáky, Katalin Burián
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Chlamydia Chlamydia trachomatis IDO interferon neutrophil polymorphonuclear (PMN) Immunologic diseases. Allergy RC581-607
Acceso en línea:	https://doaj.org/article/34085d989e0e45c2aac7cd1d4117ce0c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:34085d989e0e45c2aac7cd1d4117ce0c
record_format	dspace
spelling	oai:doaj.org-article:34085d989e0e45c2aac7cd1d4117ce0c2021-11-08T07:09:51ZIndoleamine 2,3-Dioxygenase Cannot Inhibit Chlamydia trachomatis Growth in HL-60 Human Neutrophil Granulocytes1664-322410.3389/fimmu.2021.717311https://doaj.org/article/34085d989e0e45c2aac7cd1d4117ce0c2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fimmu.2021.717311/fullhttps://doaj.org/toc/1664-3224AimsNeutrophil 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.MethodsGlobal 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).ResultsOur 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.ConclusionsIDO 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.Dezső P. VirokFerenc TömösiAnikó Keller-PintérKitti SzabóAnita BogdanovSzilárd PoliskaZsolt RázgaBella BruszelZsuzsanna CsehDávid KókaiDóra ParóczaiValéria EndrészTamás JanákyKatalin BuriánFrontiers Media S.A.articleChlamydiaChlamydia trachomatisIDOinterferonneutrophilpolymorphonuclear (PMN)Immunologic diseases. AllergyRC581-607ENFrontiers in Immunology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Chlamydia Chlamydia trachomatis IDO interferon neutrophil polymorphonuclear (PMN) Immunologic diseases. Allergy RC581-607
spellingShingle	Chlamydia Chlamydia trachomatis IDO interferon neutrophil polymorphonuclear (PMN) Immunologic diseases. Allergy RC581-607 Dezső P. Virok Ferenc Tömösi Anikó Keller-Pintér Kitti Szabó Anita Bogdanov Szilárd Poliska Zsolt Rázga Bella Bruszel Zsuzsanna Cseh Dávid Kókai Dóra Paróczai Valéria Endrész Tamás Janáky Katalin Burián Indoleamine 2,3-Dioxygenase Cannot Inhibit Chlamydia trachomatis Growth in HL-60 Human Neutrophil Granulocytes
description	AimsNeutrophil 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.MethodsGlobal 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).ResultsOur 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.ConclusionsIDO 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.
format	article
author	Dezső P. Virok Ferenc Tömösi Anikó Keller-Pintér Kitti Szabó Anita Bogdanov Szilárd Poliska Zsolt Rázga Bella Bruszel Zsuzsanna Cseh Dávid Kókai Dóra Paróczai Valéria Endrész Tamás Janáky Katalin Burián
author_facet	Dezső P. Virok Ferenc Tömösi Anikó Keller-Pintér Kitti Szabó Anita Bogdanov Szilárd Poliska Zsolt Rázga Bella Bruszel Zsuzsanna Cseh Dávid Kókai Dóra Paróczai Valéria Endrész Tamás Janáky Katalin Burián
author_sort	Dezső P. Virok
title	Indoleamine 2,3-Dioxygenase Cannot Inhibit Chlamydia trachomatis Growth in HL-60 Human Neutrophil Granulocytes
title_short	Indoleamine 2,3-Dioxygenase Cannot Inhibit Chlamydia trachomatis Growth in HL-60 Human Neutrophil Granulocytes
title_full	Indoleamine 2,3-Dioxygenase Cannot Inhibit Chlamydia trachomatis Growth in HL-60 Human Neutrophil Granulocytes
title_fullStr	Indoleamine 2,3-Dioxygenase Cannot Inhibit Chlamydia trachomatis Growth in HL-60 Human Neutrophil Granulocytes
title_full_unstemmed	Indoleamine 2,3-Dioxygenase Cannot Inhibit Chlamydia trachomatis Growth in HL-60 Human Neutrophil Granulocytes
title_sort	indoleamine 2,3-dioxygenase cannot inhibit chlamydia trachomatis growth in hl-60 human neutrophil granulocytes
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/34085d989e0e45c2aac7cd1d4117ce0c
work_keys_str_mv	AT dezsopvirok indoleamine23dioxygenasecannotinhibitchlamydiatrachomatisgrowthinhl60humanneutrophilgranulocytes AT ferenctomosi indoleamine23dioxygenasecannotinhibitchlamydiatrachomatisgrowthinhl60humanneutrophilgranulocytes AT anikokellerpinter indoleamine23dioxygenasecannotinhibitchlamydiatrachomatisgrowthinhl60humanneutrophilgranulocytes AT kittiszabo indoleamine23dioxygenasecannotinhibitchlamydiatrachomatisgrowthinhl60humanneutrophilgranulocytes AT anitabogdanov indoleamine23dioxygenasecannotinhibitchlamydiatrachomatisgrowthinhl60humanneutrophilgranulocytes AT szilardpoliska indoleamine23dioxygenasecannotinhibitchlamydiatrachomatisgrowthinhl60humanneutrophilgranulocytes AT zsoltrazga indoleamine23dioxygenasecannotinhibitchlamydiatrachomatisgrowthinhl60humanneutrophilgranulocytes AT bellabruszel indoleamine23dioxygenasecannotinhibitchlamydiatrachomatisgrowthinhl60humanneutrophilgranulocytes AT zsuzsannacseh indoleamine23dioxygenasecannotinhibitchlamydiatrachomatisgrowthinhl60humanneutrophilgranulocytes AT davidkokai indoleamine23dioxygenasecannotinhibitchlamydiatrachomatisgrowthinhl60humanneutrophilgranulocytes AT doraparoczai indoleamine23dioxygenasecannotinhibitchlamydiatrachomatisgrowthinhl60humanneutrophilgranulocytes AT valeriaendresz indoleamine23dioxygenasecannotinhibitchlamydiatrachomatisgrowthinhl60humanneutrophilgranulocytes AT tamasjanaky indoleamine23dioxygenasecannotinhibitchlamydiatrachomatisgrowthinhl60humanneutrophilgranulocytes AT katalinburian indoleamine23dioxygenasecannotinhibitchlamydiatrachomatisgrowthinhl60humanneutrophilgranulocytes
_version_	1718442892382437376

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

Ejemplares similares