High expression of IDO1 and TGF-β1 during recurrence and post infection clearance with Chlamydia trachomatis, are independent of host IFN-γ response

Noa Ziklo; Wilhelmina M Huston; Kuong Taing; Peter Timms

doi:10.1186/s12879-019-3843-4

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High expression of IDO1 and TGF-β1 during recurrence and post infection clearance with Chlamydia trachomatis, are independent of host IFN-γ response

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High expression of IDO1 and TGF-β1 during recurrence and post infection clearance with Chlamydia trachomatis, are independent of host IFN-γ response

Noa Ziklo, Wilhelmina M Huston, Kuong Taing and Peter Timms

BMC Infectious Diseases, Vol.19, 218

2019

DOI: https://doi.org/10.1186/s12879-019-3843-4

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Abstract

chlamydia trachomatis

indoleamine 2,3-dioxygenase

interferon-gamma

tryptophan

kynurenine

regulatory immune response

Background: Chlamydia trachomatis infections in women continue to be a major public health concern due to their high prevalence and consequent reproductive morbidities. While antibiotics are usually efficient to clear the Chlamydia, repeat infections are common and may contribute to pathological outcomes. Interferon-gamma (IFN-γ)-mediated immunity has been suggested to be protective against reinfection, and represent an important anti-chlamydial agent, primarily via the induction of indoleamine-2,3 dioxygenase 1 (IDO1) enzyme. IDO1 catalyzes the degradation of tryptophan, which can eliminate C. trachomatis infection in vitro. Here, we sought to measure IDO1 expression levels and related immune markers during different C. trachomatis infection statuses (repeated vs single infection vs post antibiotic treatment), in vitro and in vivo.Methods: In this study, we measured the expression levels of IDO1 and immune regulatory markers, transforming growth factor β1 (TGF-β1) and forkhead box P3 (FoxP3), in vaginal swab samples of C. trachomatis-infected women, with either single or repeated infection. In addition, we used an in vitro co-culture model of endometrial carcinoma cell-line and peripheral blood mononuclear cells (PBMCs) to measure the same immune markers.Results: We found that in women with repeated C. trachomatis infections vaginal IDO1 and TGF-β1 expression levels were significantly increased. Whereas, women who cleared their infection post antibiotic treatment, had increased levels of IDO1 and TGF-β1, as well as FoxP3. Similarly, using the in vitro model, we found significant upregulation of IDO1 and TGF-β1 levels in the co-culture infected with C. trachomatis. Furthermore, we found that in PBMCs infected with C. trachomatis there was a significant upregulation in IDO1 levels, which was independent of IFN-γ. In fact, C. trachomatis infection in PBMCs failed to induce IFN-γ levels in comparison to the uninfected culture.Conclusions: Our data provide evidence for a regulatory immune response comprised of IDO1, TGF-β1 and FoxP3 in women post antibiotic treatment. In this study, we demonstrated a significant increase in IDO1 expression levels in response to C. trachomatis infection, both in vivo and in vitro, without elevated IFN-γ levels. This study implicates IDO1 and TGF-β1 as part of the immune response to repeated C. trachomatis infections, independently of IFN-γ.

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Title: High expression of IDO1 and TGF-β1 during recurrence and post infection clearance with Chlamydia trachomatis, are independent of host IFN-γ response
Authors: Noa Ziklo (Author) - University of the Sunshine Coast - School of Science & Engineering
Wilhelmina M Huston (Author) - University of Technology Sydney
Kuong Taing (Author) - Sunshine Coast Sexual Health and HIV Service
Peter Timms (Author) - University of the Sunshine Coast - School of Science & Engineering
Publication details: BMC Infectious Diseases, Vol.19, 218; 11
Publisher: BioMed Central Ltd.
Date published: 2019
DOI: 10.1186/s12879-019-3843-4
ISSN: 1471-2334
Copyright note: Copyright © The Author(s). 2019 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Organisation Unit: School of Science and Engineering - Legacy; University of the Sunshine Coast, Queensland; Centre for Bioinnovation
Language: English
Record Identifier: 99450988502621
Output Type: Journal article

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