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The biology of how circumcision reduces HIV susceptibility: broader implications for the prevention field
Circumcision reduces heterosexual HIV-1 acquisition in men by at least 60%. However, the biological mechanisms by which circumcision is protective remain incompletely understood. We test the hypothesis that the sub-preputial microenvironment created by the foreskin drives immune activation in adjace...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594533/ https://www.ncbi.nlm.nih.gov/pubmed/28893286 http://dx.doi.org/10.1186/s12981-017-0167-6 |
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author | Prodger, Jessica L. Kaul, Rupert |
author_facet | Prodger, Jessica L. Kaul, Rupert |
author_sort | Prodger, Jessica L. |
collection | PubMed |
description | Circumcision reduces heterosexual HIV-1 acquisition in men by at least 60%. However, the biological mechanisms by which circumcision is protective remain incompletely understood. We test the hypothesis that the sub-preputial microenvironment created by the foreskin drives immune activation in adjacent foreskin tissues, facilitating HIV-1 infection through a combination of epithelial barrier disruption, enhanced dendritic cell maturation, and the recruitment/activation of neutrophils and susceptible CD4 T cell subsets such as Th17 cells. Furthermore, we provide evidence that the genital microbiome may be an important driver of this immune activation. This suggests that new modalities to reduce genital immune activation and/or alter the genital microbiome, used alone or in combination with topical microbicides, may be of significant benefit to HIV prevention. |
format | Online Article Text |
id | pubmed-5594533 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-55945332017-09-14 The biology of how circumcision reduces HIV susceptibility: broader implications for the prevention field Prodger, Jessica L. Kaul, Rupert AIDS Res Ther Review Circumcision reduces heterosexual HIV-1 acquisition in men by at least 60%. However, the biological mechanisms by which circumcision is protective remain incompletely understood. We test the hypothesis that the sub-preputial microenvironment created by the foreskin drives immune activation in adjacent foreskin tissues, facilitating HIV-1 infection through a combination of epithelial barrier disruption, enhanced dendritic cell maturation, and the recruitment/activation of neutrophils and susceptible CD4 T cell subsets such as Th17 cells. Furthermore, we provide evidence that the genital microbiome may be an important driver of this immune activation. This suggests that new modalities to reduce genital immune activation and/or alter the genital microbiome, used alone or in combination with topical microbicides, may be of significant benefit to HIV prevention. BioMed Central 2017-09-12 /pmc/articles/PMC5594533/ /pubmed/28893286 http://dx.doi.org/10.1186/s12981-017-0167-6 Text en © The Author(s) 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Review Prodger, Jessica L. Kaul, Rupert The biology of how circumcision reduces HIV susceptibility: broader implications for the prevention field |
title | The biology of how circumcision reduces HIV susceptibility: broader implications for the prevention field |
title_full | The biology of how circumcision reduces HIV susceptibility: broader implications for the prevention field |
title_fullStr | The biology of how circumcision reduces HIV susceptibility: broader implications for the prevention field |
title_full_unstemmed | The biology of how circumcision reduces HIV susceptibility: broader implications for the prevention field |
title_short | The biology of how circumcision reduces HIV susceptibility: broader implications for the prevention field |
title_sort | biology of how circumcision reduces hiv susceptibility: broader implications for the prevention field |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5594533/ https://www.ncbi.nlm.nih.gov/pubmed/28893286 http://dx.doi.org/10.1186/s12981-017-0167-6 |
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