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

Autor: Wilhelmina M. Huston, Peter Timms, Kuong Taing, Noa Ziklo
Jazyk: angličtina
Rok vydání: 2019
Předmět:
Adult
0301 basic medicine
medicine.medical_specialty
Indoleamine 2
3-dioxygenase
medicine.drug_class
030106 microbiology
Antibiotics
Chlamydia trachomatis
medicine.disease_cause
Cell Line
lcsh:Infectious and parasitic diseases
Transforming Growth Factor beta1
Young Adult
03 medical and health sciences
Interferon-gamma
0302 clinical medicine
Medical microbiology
Immune system
Recurrence
In vivo
Immunity
medicine
Humans
Indoleamine-Pyrrole 2
3
-Dioxygenase
lcsh:RC109-216
030212 general & internal medicine
Kynurenine
Chlamydia
business.industry
Tryptophan
FOXP3
Forkhead Transcription Factors
Regulatory immune response
Chlamydia Infections
medicine.disease
Coculture Techniques
Anti-Bacterial Agents
Up-Regulation
Infectious Diseases
Vagina
Immunology
Leukocytes
Mononuclear
Female
business
Research Article
Zdroj: BMC Infectious Diseases, Vol 19, Iss 1, Pp 1-11 (2019)
BMC Infectious Diseases
ISSN: 1471-2334
DOI: 10.1186/s12879-019-3843-4
Popis: 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. Electronic supplementary material The online version of this article (10.1186/s12879-019-3843-4) contains supplementary material, which is available to authorized users.
Databáze: OpenAIRE
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