Matrix Metalloproteinases Expressed in Response to Bacterial Vaginosis Disrupt the Endocervical Epithelium, Increasing Transmigration of HIV
| Autor: | Michael Deichen, Lisa Newberry, Michelle D. Cherne, Alexander M. Cole, Amy L. Cole, Mary Schmidt-Owens |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Immunology Human immunodeficiency virus (HIV) Matrix metalloproteinase medicine.disease_cause Microbiology Epithelium Permeability Virus Endometrium 03 medical and health sciences 0302 clinical medicine Cell Movement medicine Humans Lymphocytes Cells Cultured Host Response and Inflammation 030219 obstetrics & reproductive medicine biology Vaginosis Bacterial Models Theoretical biology.organism_classification medicine.disease Matrix Metalloproteinases 030104 developmental biology Infectious Diseases medicine.anatomical_structure Cell culture HIV-1 Female Parasitology Bacterial vaginosis Bacteria Endocervix |
| Zdroj: | Infect Immun |
| ISSN: | 1098-5522 0019-9567 |
| DOI: | 10.1128/iai.00041-20 |
| Popis: | Bacterial vaginosis (BV), a disorder of the female reproductive tract (FRT) in which a healthy Lactobacillus-dominant microflora is replaced by BV-associated bacteria (BVAB), can significantly increase the incidence of human immunodeficiency virus (HIV) acquisition. Discerning the effect of BV on the mucosal epithelium of the FRT may yield novel preventatives and therapeutics for HIV infection. Here, we investigated barrier dysfunction of the endocervix by host-derived factors, secreted in response to BV, as a potential cause of HIV infection. Using a polarized endocervical cell culture system, we determined that conditioned media (CM) from endocervical cells cocultured with BVAB (endocervical+BVAB CM), as well as cervicovaginal fluid (CVF) from women with BV, disrupted epithelial polarization. We assessed host matrix metalloproteinases (MMPs) as the BV-associated secreted factors which disrupt the endocervical epithelium. MMPs were overexpressed in endocervical+BVAB CM and CVF from women with BV and were capable of disrupting endocervical epithelial polarization. When we cocultured polarized endocervical cells with HIV-1-infected lymphocyte-derived cells, we discovered endocervical+BVAB CM and MMPs significantly increased the transmigration of virus through the epithelium, and treatment with an MMP inhibitor decreased these effects. When we examined the effect of CVF on HIV-1 transmigration through endocervical epithelium, we demonstrated that CVF samples with greater concentrations of BV-associated MMPs increased viral transmigration. Our results suggest MMPs increase HIV-1 infection by disrupting the endocervical epithelium, permitting transmigration of virus through the epithelium to infect underlying target cells. |
| Databáze: | OpenAIRE |
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