Extracellular vesicles from vaginal Gardnerella vaginalis and Mobiluncus mulieris contain distinct proteomic cargo and induce inflammatory pathways
Summary Colonization of the vaginal space with bacteria such as Gardnerella vaginalis and Mobiluncus mulieris is associated with increased risk for STIs, bacterial vaginosis, and preterm birth, while Lactobacillus crispatus is associated with optimal reproductive health. Although host-microbe intera...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2024-03-01
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| Series: | npj Biofilms and Microbiomes |
| Online Access: | https://doi.org/10.1038/s41522-024-00502-y |
| _version_ | 1827310331571994624 |
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| author | Andrea Joseph Lauren Anton Yuxia Guan Briana Ferguson Isabella Mirro Nova Meng Michael France Jacques Ravel Michal A. Elovitz |
| author_facet | Andrea Joseph Lauren Anton Yuxia Guan Briana Ferguson Isabella Mirro Nova Meng Michael France Jacques Ravel Michal A. Elovitz |
| author_sort | Andrea Joseph |
| collection | DOAJ |
| description | Summary Colonization of the vaginal space with bacteria such as Gardnerella vaginalis and Mobiluncus mulieris is associated with increased risk for STIs, bacterial vaginosis, and preterm birth, while Lactobacillus crispatus is associated with optimal reproductive health. Although host-microbe interactions are hypothesized to contribute to reproductive health and disease, the bacterial mediators that are critical to this response remain unclear. Bacterial extracellular vesicles (bEVs) are proposed to participate in host-microbe communication by providing protection of bacterial cargo, delivery to intracellular targets, and ultimately induction of immune responses from the host. We evaluated the proteome of bEVs produced in vitro from G. vaginalis, M. mulieris, and L. crispatus, identifying specific proteins of immunologic interest. We found that bEVs from each bacterial species internalize within cervical and vaginal epithelial cells, and that epithelial and immune cells express a multi-cytokine response when exposed to bEVs from G. vaginalis and M. mulieris but not L. crispatus. Further, we demonstrate that the inflammatory response induced by G. vaginalis and M. mulieris bEVs is TLR2-specific. Our results provide evidence that vaginal bacteria communicate with host cells through secreted bEVs, revealing a mechanism by which bacteria lead to adverse reproductive outcomes associated with inflammation. Elucidating host-microbe interactions in the cervicovaginal space will provide further insight into the mechanisms contributing to microbiome-mediated adverse outcomes and may reveal new therapeutic targets. |
| first_indexed | 2024-04-24T19:59:09Z |
| format | Article |
| id | doaj.art-522f7d99b62b40bb86e5c2915289266a |
| institution | Directory Open Access Journal |
| issn | 2055-5008 |
| language | English |
| last_indexed | 2024-04-24T19:59:09Z |
| publishDate | 2024-03-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | npj Biofilms and Microbiomes |
| spelling | doaj.art-522f7d99b62b40bb86e5c2915289266a2024-03-24T12:12:08ZengNature Portfolionpj Biofilms and Microbiomes2055-50082024-03-0110111210.1038/s41522-024-00502-yExtracellular vesicles from vaginal Gardnerella vaginalis and Mobiluncus mulieris contain distinct proteomic cargo and induce inflammatory pathwaysAndrea Joseph0Lauren Anton1Yuxia Guan2Briana Ferguson3Isabella Mirro4Nova Meng5Michael France6Jacques Ravel7Michal A. Elovitz8Women’s Biomedical Research Institute, Icahn School of Medicine at Mount Sinai, New YorkCenter for Research on Reproduction and Women’s Health, University of PennsylvaniaCenter for Research on Reproduction and Women’s Health, University of PennsylvaniaCenter for Research on Reproduction and Women’s Health, University of PennsylvaniaCenter for Research on Reproduction and Women’s Health, University of PennsylvaniaCenter for Research on Reproduction and Women’s Health, University of PennsylvaniaInstitute for Genome Sciences, University of Maryland School of MedicineInstitute for Genome Sciences, University of Maryland School of MedicineWomen’s Biomedical Research Institute, Icahn School of Medicine at Mount Sinai, New YorkSummary Colonization of the vaginal space with bacteria such as Gardnerella vaginalis and Mobiluncus mulieris is associated with increased risk for STIs, bacterial vaginosis, and preterm birth, while Lactobacillus crispatus is associated with optimal reproductive health. Although host-microbe interactions are hypothesized to contribute to reproductive health and disease, the bacterial mediators that are critical to this response remain unclear. Bacterial extracellular vesicles (bEVs) are proposed to participate in host-microbe communication by providing protection of bacterial cargo, delivery to intracellular targets, and ultimately induction of immune responses from the host. We evaluated the proteome of bEVs produced in vitro from G. vaginalis, M. mulieris, and L. crispatus, identifying specific proteins of immunologic interest. We found that bEVs from each bacterial species internalize within cervical and vaginal epithelial cells, and that epithelial and immune cells express a multi-cytokine response when exposed to bEVs from G. vaginalis and M. mulieris but not L. crispatus. Further, we demonstrate that the inflammatory response induced by G. vaginalis and M. mulieris bEVs is TLR2-specific. Our results provide evidence that vaginal bacteria communicate with host cells through secreted bEVs, revealing a mechanism by which bacteria lead to adverse reproductive outcomes associated with inflammation. Elucidating host-microbe interactions in the cervicovaginal space will provide further insight into the mechanisms contributing to microbiome-mediated adverse outcomes and may reveal new therapeutic targets.https://doi.org/10.1038/s41522-024-00502-y |
| spellingShingle | Andrea Joseph Lauren Anton Yuxia Guan Briana Ferguson Isabella Mirro Nova Meng Michael France Jacques Ravel Michal A. Elovitz Extracellular vesicles from vaginal Gardnerella vaginalis and Mobiluncus mulieris contain distinct proteomic cargo and induce inflammatory pathways npj Biofilms and Microbiomes |
| title | Extracellular vesicles from vaginal Gardnerella vaginalis and Mobiluncus mulieris contain distinct proteomic cargo and induce inflammatory pathways |
| title_full | Extracellular vesicles from vaginal Gardnerella vaginalis and Mobiluncus mulieris contain distinct proteomic cargo and induce inflammatory pathways |
| title_fullStr | Extracellular vesicles from vaginal Gardnerella vaginalis and Mobiluncus mulieris contain distinct proteomic cargo and induce inflammatory pathways |
| title_full_unstemmed | Extracellular vesicles from vaginal Gardnerella vaginalis and Mobiluncus mulieris contain distinct proteomic cargo and induce inflammatory pathways |
| title_short | Extracellular vesicles from vaginal Gardnerella vaginalis and Mobiluncus mulieris contain distinct proteomic cargo and induce inflammatory pathways |
| title_sort | extracellular vesicles from vaginal gardnerella vaginalis and mobiluncus mulieris contain distinct proteomic cargo and induce inflammatory pathways |
| url | https://doi.org/10.1038/s41522-024-00502-y |
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