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Sex hormones selectively impact the endocervical mucosal microenvironment: implications for HIV transmission

dc.contributor.authorGoode, Diana
dc.contributor.authorAravantinou, Meropi
dc.contributor.authorJarl, Sebastian
dc.contributor.authorTruong, Rosaline
dc.contributor.authorDerby, Nina
dc.contributor.authorGuerra Pérez, Natalia
dc.contributor.authorKenney, Jessica .
dc.contributor.authorBlanchard, James
dc.contributor.authorGettie, Agegnehu
dc.contributor.authorRobbiani, Melissa
dc.contributor.authorMartinelli, Elena
dc.date.accessioned2024-02-01T13:43:00Z
dc.date.available2024-02-01T13:43:00Z
dc.date.issued2014
dc.description.abstractSeveral studies suggest that progesterone and estrogens may affect HIV transmission in different, possibly opposing ways. Nonetheless, a direct comparison of their effects on the mucosal immune system has never been done. We hypothesize that sex hormones might impact the availability of cells and immune factors important in early stages of mucosal transmission, and, in doing so influence the risk of HIV acquisition. To test this hypothesis, we employed 15 ovarectomized rhesus macaques: 5 were treated with Depot Medroxy Progesterone Acetate (DMPA), 6 with 17-β estradiol (E2) and 4 were left untreated. All animals were euthanized 5 weeks after the initiation of hormone treatment, a time post-DMPA injection associated with high susceptibility to SIV infection. We found that DMPA-treated macaques exhibited higher expression of integrin α4β7 (α4β7) on CD4+ T cells, the gut homing receptor and a marker of cells highly susceptible to HIV, in the endocervix than did the E2-treated animals. In contrast, the frequency of CCR5+ CD4+ T cells in DMPA-treated macaques was higher than in the E2-treated group in vaginal tissue, but lower in endocervix. α4β7 expression on dendritic cells (DCs) was higher in the DMPA-treated group in the endocervical tissue, but lower in vaginal tissue and on blood DCs compared with the E2-treated animals. Soluble MAdCAM-1, the α4β7 ligand, was present in the vaginal fluids of the control and E2-treated groups, but absent in the fluids from DMPA-treated animals. Both hormones modulated the expression and release of inflammatory factors and modified the distribution of sialomucins in the endocervix. In summary, we found that sex hormones profoundly impact mucosal immune factors that are directly implicated in HIV transmission. The effect is particularly significant in the endocervix. This may increase our understanding of the potential hormone-driven modulation of HIV susceptibility and potentially guide contraceptive policies in high-risk settings.
dc.description.departmentDepto. de Genética, Fisiología y Microbiología
dc.description.facultyFac. de Ciencias Biológicas
dc.description.refereedTRUE
dc.description.statuspub
dc.identifier.citationGoode, Diana, et al. «Sex Hormones Selectively Impact the Endocervical Mucosal Microenvironment: Implications for HIV Transmission». PLoS ONE, editado por Derya Unutmaz, vol. 9, n.o 5, mayo de 2014, p. e97767. https://doi.org/10.1371/journal.pone.0097767.
dc.identifier.doi10.1371/journal.pone.0097767
dc.identifier.issn1932-6203
dc.identifier.officialurlhttps://doi.org/10.1371/journal.pone.0097767
dc.identifier.relatedurlhttps://journals.plos.org/plosone/article?id=10.1371/journal.pone.0097767
dc.identifier.urihttps://hdl.handle.net/20.500.14352/97773
dc.issue.number5
dc.journal.titlePloS one
dc.language.isoeng
dc.publisherPublic Library of Science
dc.rights.accessRightsopen access
dc.subject.ucmBiología
dc.subject.unesco2412 Inmunología
dc.titleSex hormones selectively impact the endocervical mucosal microenvironment: implications for HIV transmission
dc.typejournal article
dc.type.hasVersionVoR
dc.volume.number9
dspace.entity.typePublication
relation.isAuthorOfPublication25551a6d-4113-4833-aa8e-85c3eee7da2d
relation.isAuthorOfPublication.latestForDiscovery25551a6d-4113-4833-aa8e-85c3eee7da2d

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