Slight Pro-Inflammatory Immunomodulation Properties of Dendritic Cells by Gardnerella vaginalis: The "Invisible Man" of Bacterial Vaginosis?

Thomas Bertran,Annie Dosgilbert,Patrick Brachet,Arlette Tridon,Bertrand Evrard,Marjolaine Vareille-Delarbre,Christiane Forestier,Marie-Paule Vasson,Julie Falenta

doi:10.1155/2016/9747480

Abstract

Bacterial vaginosis (BV), the most common genital infection in reproductive-aged women, is associated with increased risk of sexually transmitted infections. Its etiology remains unclear, especially the role of Gardnerella (G.) vaginalis, an anaerobic bacterium characteristic of the BV-alteration of the vaginal ecosystem. In the genital mucosa, dendritic cells (DCs) sense bacteria of the microenvironment via receptors and then orchestrate the immune response by induction of different T cell subtypes. We investigated the interactions between G. vaginalis and human monocyte-derived DCs using a wide range of bacterial concentrations (multiplicity of infection from 0.01 to 100), and the effects of this pathogen on PHA-induced lymphocyte proliferation. As observed by electron microscopy and cytometry, G. vaginalis reduced the internalization ability of DCs by forming extracellular clusters and induced neither DC maturation, nor DC secretion of cytokines, except at the highest dose with a very early DC maturation state. The same profile was observed on lymphocytes with significant increases of proliferation and cytokine secretion only at the highest bacterial concentration. Our findings indicate that G. vaginalis possesses slight immune-stimulating activities against DCs and T cells, reflecting thus a defective inflammatory response and giving rise to the atypical, non- or low-grade, inflammatory clinical disease profile.

Highlights

Bacterial vaginosis (BV) is the most common low genital infection among reproductive-aged women, with a prevalence of 29% among 14- to 49-year-old US women and almost 40% in individuals at high risk for sexually transmitted infections (STIs) [1]
dendritic cells (DCs) can interact with luminal microorganisms, either indirectly via epithelial transport mechanisms or directly via dendrites extended across epithelial cells that take up bacteria from the vaginal lumen [31, 32]
As BV is characterized by an imbalance of the normal H2O2-producing Lactobacillus flora toward a polymorphic anaerobic flora with predominant G. vaginalis, it is likely that the pattern recognition receptors (PRRs) of vaginal DCs are subsequently affected by this alteration

Summary

Introduction

Bacterial vaginosis (BV) is the most common low genital infection among reproductive-aged women, with a prevalence of 29% among 14- to 49-year-old US women and almost 40% in individuals at high risk for sexually transmitted infections (STIs) [1]. BV increases women’s risk of acquiring STIs, HIV infections [4, 5]. One-half of BV-positive women are asymptomatic while the others suffer only from mild symptoms, such as homogeneous white vaginal discharge and amine (fishy) odor [6]. These signs are associated with a vaginal pH > 4.5 and the presence of characteristic “clue cells” on microscopic examination.

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Results

Conclusion