Gardnerella vaginalis alters cervicovaginal epithelial cell function through microbe-specific immune responses
Abstract Background The cervicovaginal (CV) microbiome is highly associated with vaginal health and disease in both pregnant and nonpregnant individuals. An overabundance of Gardnerella vaginalis (G. vaginalis) in the CV space is commonly associated with adverse reproductive outcomes including bacte...
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Microbiome |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40168-022-01317-9 |
| _version_ | 1811315147737661440 |
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| author | Lauren Anton Briana Ferguson Elliot S. Friedman Kristin D. Gerson Amy G. Brown Michal A. Elovitz |
| author_facet | Lauren Anton Briana Ferguson Elliot S. Friedman Kristin D. Gerson Amy G. Brown Michal A. Elovitz |
| author_sort | Lauren Anton |
| collection | DOAJ |
| description | Abstract Background The cervicovaginal (CV) microbiome is highly associated with vaginal health and disease in both pregnant and nonpregnant individuals. An overabundance of Gardnerella vaginalis (G. vaginalis) in the CV space is commonly associated with adverse reproductive outcomes including bacterial vaginosis (BV), sexually transmitted diseases, and preterm birth, while the presence of Lactobacillus spp. is often associated with reproductive health. While host-microbial interactions are hypothesized to contribute to CV health and disease, the mechanisms by which these interactions regulate CV epithelial function remain largely unknown. Results Using an in vitro co-culture model, we assessed the effects of Lactobacillus crispatus (L. crispatus) and G. vaginalis on the CV epithelial barrier, the immune mediators that could be contributing to decreased barrier integrity and the immune signaling pathways regulating the immune response. G. vaginalis, but not L. crispatus, significantly increased epithelial cell death and decreased epithelial barrier integrity in an epithelial cell-specific manner. A G. vaginalis-mediated epithelial immune response including NF-κB activation and proinflammatory cytokine release was initiated partially through TLR2-dependent signaling pathways. Additionally, investigation of the cytokine immune profile in human CV fluid showed distinctive clustering of cytokines by Gardnerella spp. abundance and birth outcome. Conclusions The results of this study show microbe-specific effects on CV epithelial function. Altered epithelial barrier function through cell death and immune-mediated mechanisms by G. vaginalis, but not L. crispatus, indicates that host epithelial cells respond to bacteria-associated signals, resulting in altered epithelial function and ultimately CV disease. Additionally, distinct immune signatures associated with Gardnerella spp. or birth outcome provide further evidence that host-microbial interactions may contribute significantly to the biological mechanisms regulating reproductive outcomes. Video Abstract |
| first_indexed | 2024-04-13T11:25:00Z |
| format | Article |
| id | doaj.art-37c6f31fc67a452685b0c91deb075f3b |
| institution | Directory Open Access Journal |
| issn | 2049-2618 |
| language | English |
| last_indexed | 2024-04-13T11:25:00Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Microbiome |
| spelling | doaj.art-37c6f31fc67a452685b0c91deb075f3b2022-12-22T02:48:43ZengBMCMicrobiome2049-26182022-08-0110112010.1186/s40168-022-01317-9Gardnerella vaginalis alters cervicovaginal epithelial cell function through microbe-specific immune responsesLauren Anton0Briana Ferguson1Elliot S. Friedman2Kristin D. Gerson3Amy G. Brown4Michal A. Elovitz5Department of Obstetrics and Gynecology, Center for Research on Reproduction and Women’s Health, Perelman School of Medicine at the University of PennsylvaniaDepartment of Obstetrics and Gynecology, Center for Research on Reproduction and Women’s Health, Perelman School of Medicine at the University of PennsylvaniaDivision of Gastroenterology and Hepatology, Perelman School of Medicine at the University of PennsylvaniaDepartment of Obstetrics and Gynecology, Center for Research on Reproduction and Women’s Health, Perelman School of Medicine at the University of PennsylvaniaDepartment of Obstetrics and Gynecology, Center for Research on Reproduction and Women’s Health, Perelman School of Medicine at the University of PennsylvaniaDepartment of Obstetrics and Gynecology, Center for Research on Reproduction and Women’s Health, Perelman School of Medicine at the University of PennsylvaniaAbstract Background The cervicovaginal (CV) microbiome is highly associated with vaginal health and disease in both pregnant and nonpregnant individuals. An overabundance of Gardnerella vaginalis (G. vaginalis) in the CV space is commonly associated with adverse reproductive outcomes including bacterial vaginosis (BV), sexually transmitted diseases, and preterm birth, while the presence of Lactobacillus spp. is often associated with reproductive health. While host-microbial interactions are hypothesized to contribute to CV health and disease, the mechanisms by which these interactions regulate CV epithelial function remain largely unknown. Results Using an in vitro co-culture model, we assessed the effects of Lactobacillus crispatus (L. crispatus) and G. vaginalis on the CV epithelial barrier, the immune mediators that could be contributing to decreased barrier integrity and the immune signaling pathways regulating the immune response. G. vaginalis, but not L. crispatus, significantly increased epithelial cell death and decreased epithelial barrier integrity in an epithelial cell-specific manner. A G. vaginalis-mediated epithelial immune response including NF-κB activation and proinflammatory cytokine release was initiated partially through TLR2-dependent signaling pathways. Additionally, investigation of the cytokine immune profile in human CV fluid showed distinctive clustering of cytokines by Gardnerella spp. abundance and birth outcome. Conclusions The results of this study show microbe-specific effects on CV epithelial function. Altered epithelial barrier function through cell death and immune-mediated mechanisms by G. vaginalis, but not L. crispatus, indicates that host epithelial cells respond to bacteria-associated signals, resulting in altered epithelial function and ultimately CV disease. Additionally, distinct immune signatures associated with Gardnerella spp. or birth outcome provide further evidence that host-microbial interactions may contribute significantly to the biological mechanisms regulating reproductive outcomes. Video Abstracthttps://doi.org/10.1186/s40168-022-01317-9CervixLactobacillus crispatusGardnerella vaginalisEpithelial barrierInflammationTLR2 |
| spellingShingle | Lauren Anton Briana Ferguson Elliot S. Friedman Kristin D. Gerson Amy G. Brown Michal A. Elovitz Gardnerella vaginalis alters cervicovaginal epithelial cell function through microbe-specific immune responses Microbiome Cervix Lactobacillus crispatus Gardnerella vaginalis Epithelial barrier Inflammation TLR2 |
| title | Gardnerella vaginalis alters cervicovaginal epithelial cell function through microbe-specific immune responses |
| title_full | Gardnerella vaginalis alters cervicovaginal epithelial cell function through microbe-specific immune responses |
| title_fullStr | Gardnerella vaginalis alters cervicovaginal epithelial cell function through microbe-specific immune responses |
| title_full_unstemmed | Gardnerella vaginalis alters cervicovaginal epithelial cell function through microbe-specific immune responses |
| title_short | Gardnerella vaginalis alters cervicovaginal epithelial cell function through microbe-specific immune responses |
| title_sort | gardnerella vaginalis alters cervicovaginal epithelial cell function through microbe specific immune responses |
| topic | Cervix Lactobacillus crispatus Gardnerella vaginalis Epithelial barrier Inflammation TLR2 |
| url | https://doi.org/10.1186/s40168-022-01317-9 |
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