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Ureaplasma parvum infection induces inflammatory changes in vaginal epithelial cells independent of sialidase

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Abstract

Background

Ureaplasma, a genus of the order Mycoplasmatales and commonly grouped with Mycoplasma as genital mycoplasma is one of the most common microbes isolated from women with infection/inflammation-associated preterm labor (PTL). Mycoplasma spp. produce sialidase that cleaves sialic acid from glycans of vaginal mucous membranes and facilitates adherence and invasion of the epithelium by pathobionts, and dysregulated immune response. However, whether Ureaplasma species can induce the production of sialidase is yet to be demonstrated. We examined U. parvum-infected vaginal epithelial cells (VECs) for the production of sialidase and pro-inflammatory cytokines.

Methods

Immortalized VECs were cultured in appropriate media and treated with U. parvum in a concentration of 1 × 105 DNA copies/ml. After 24 h of treatment, cells and media were harvested. To confirm infection and cell uptake, immunocytochemistry for multi-banded antigen (MBA) was performed. Pro-inflammatory cytokine production and protein analysis for sialidase confirmed pro-labor pathways.

Results

Infection of VECs was confirmed by the presence of intracellular MBA. Western blot analysis showed no significant increase in sialidase expression from U. parvum-treated VECs compared to uninfected cells. However, U. parvum infection induced 2-3-fold increased production of GM-CSF (p = 0.03), IL-6 (p = 0.01), and IL-8 (p = 0.01) in VECs compared to controls.

Conclusion

U. parvum infection of VECs induced inflammatory imbalance associated with vaginal dysbiosis but did not alter sialidase expression at the cellular level. These data suggest that U. parvum’s pathogenic effect could be propagated by locally produced pro-inflammatory cytokines and, unlike other genital mycoplasmas, may be independent of sialidase.

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Acknowledgements

We would like to thank the entire staff and students of The Menon’s lab at the Division of Basic Science and Translational Research, Department of Obstetrics and Gynaecology, University of Texas Medical Branch (UTMB), Texas, USA for their moral and technical support towards the success of Emmanuel’s visit and this project.

Funding

This work was funded by the Society for Reproductive Investigation ​​International Training Grant 2020–2021 awarded to Dr Emmanuel Amabebe to visit Professor Ramkumar Menon’s laboratory at the Division of Basic Science and Translational Research, Department of Obstetrics and Gynecology, University of Texas Medical Branch (UTMB), Texas, USA.

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Authors and Affiliations

  1. Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK

    Emmanuel Amabebe & Dilly O. C. Anumba

  2. Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, USA

    Lauren S. Richardson, Giovana Fernanda Cosi Bento, Enkhtuya Radnaa, Talar Kechichian & Ramkumar Menon

  3. Department of Pathology, Universidade Estadual Paulista, Botucatu Medical School, Botucatu, Brazil

    Giovana Fernanda Cosi Bento

  4. Academic Unit of Reproductive and Developmental Medicine, Department of Oncology and Metabolism, The University of Sheffield, 4th Floor, Jessop Wing, Tree Root Walk, S10 2SF, Sheffield, UK

    Dilly O. C. Anumba

  5. Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, 301 University Blvd, 77555-1062, Galveston, TX, USA

    Ramkumar Menon

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  1. Emmanuel Amabebe
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Contributions

The study was conceived by EA, DA, LR, RM. The experiments and data analysis were conducted by EA, LR, GB, ER, TK and supervised by RM. The initial draft of the manuscript was written by EA, LR, GB, ER, and edited by all authors. All authors reviewed and approved the final draft of the manuscript for submission.

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Correspondence to Ramkumar Menon or Dilly O. C. Anumba.

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Amabebe, E., Richardson, L.S., Bento, G.F.C. et al. Ureaplasma parvum infection induces inflammatory changes in vaginal epithelial cells independent of sialidase. Mol Biol Rep 50, 3035–3043 (2023). https://doi.org/10.1007/s11033-022-08183-6

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