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Gardnerella vaginalis alters cervicovaginal epithelial cell function through microbe-specific immune responses
Lauren Anton1, Briana Ferguson2, Elliot S Friedman3
1Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women's Health, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA. lanton@pennmedicine.upenn.edu.
Microbiome
|August 3, 2022
Summary
Gardnerella vaginalis disrupts the cervicovaginal epithelial barrier and triggers an immune response, unlike Lactobacillus crispatus. This microbe-specific effect impacts reproductive health and birth outcomes.
Area of Science:
- Reproductive biology
- Microbiome research
- Immunology
Background:
- The cervicovaginal (CV) microbiome influences vaginal health and disease.
- Gardnerella vaginalis (G. vaginalis) overabundance is linked to adverse reproductive outcomes like bacterial vaginosis (BV) and preterm birth.
- Lactobacillus spp. presence is generally associated with reproductive health, but mechanisms of host-microbial interaction remain unclear.
Purpose of the Study:
- To investigate the effects of L. crispatus and G. vaginalis on CV epithelial barrier function.
- To identify immune mediators and signaling pathways involved in CV epithelial responses.
- To explore the relationship between CV cytokine profiles, Gardnerella spp. abundance, and birth outcomes.
Main Methods:
- Utilized an in vitro co-culture model to assess microbe-epithelial interactions.
- Examined epithelial cell death and barrier integrity.
- Analyzed immune responses, including NF-κB activation, cytokine release, and TLR2-dependent signaling.
- Profiled cytokines in human CV fluid.
Main Results:
- G. vaginalis, but not L. crispatus, significantly increased epithelial cell death and decreased barrier integrity.
- G. vaginalis induced an epithelial immune response involving NF-κB activation and pro-inflammatory cytokine release, partly via TLR2 signaling.
- Human CV fluid analysis revealed distinct cytokine patterns correlating with Gardnerella spp. abundance and birth outcomes.
Conclusions:
- Microbes exert specific effects on CV epithelial function.
- G. vaginalis impairs epithelial barrier integrity through cell death and immune activation, contributing to CV disease.
- Distinct immune signatures linked to Gardnerella spp. and birth outcomes highlight the role of host-microbial interactions in reproductive health.
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