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Seminal plasma induces inflammation and enhances HIV-1 replication in human cervical tissue explants

The most immediate and evident effect of mucosal exposure to semen in vivo is a local release of proinflammatory mediators accompanied by an influx of leukocytes into the female genital mucosa (FGM). The implication of such response in HIV-1 transmission has never been addressed due to limitations o...

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Autores principales: Introini, Andrea, Boström, Stéphanie, Bradley, Frideborg, Gibbs, Anna, Glaessgen, Axel, Tjernlund, Annelie, Broliden, Kristina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453613/
https://www.ncbi.nlm.nih.gov/pubmed/28542587
http://dx.doi.org/10.1371/journal.ppat.1006402
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author Introini, Andrea
Boström, Stéphanie
Bradley, Frideborg
Gibbs, Anna
Glaessgen, Axel
Tjernlund, Annelie
Broliden, Kristina
author_facet Introini, Andrea
Boström, Stéphanie
Bradley, Frideborg
Gibbs, Anna
Glaessgen, Axel
Tjernlund, Annelie
Broliden, Kristina
author_sort Introini, Andrea
collection PubMed
description The most immediate and evident effect of mucosal exposure to semen in vivo is a local release of proinflammatory mediators accompanied by an influx of leukocytes into the female genital mucosa (FGM). The implication of such response in HIV-1 transmission has never been addressed due to limitations of currently available experimental models. Using human tissue explants from the uterine cervix, we developed a system of mucosal exposure to seminal plasma (SP) that supports HIV-1 replication. Treatment of ectocervical explants with SP resulted in the upregulation of inflammatory and growth factors, including IL-6, TNF, CCL5, CCL20, CXCL1, and CXCL8, and IL1A, CSF2, IL7, PTGS2, as evaluated by measuring protein levels in explant conditioned medium (ECM) and gene expression in tissue. SP treatment was also associated with increased recruitment of monocytes and neutrophils, as observed upon incubation of peripheral blood leukocytes with ECM in a transwell system. To evaluate the impact of the SP-mediated response on local susceptibility to HIV-1, we infected ectocervical explants with the CCR5-tropic variant HIV-1(BaL) either in the presence of SP, or after explant pre-incubation with SP. In both experimental settings SP enhanced virus replication as evaluated by HIV-1 p24(gag) released in explant culture medium over time, as well as by HIV-1 DNA quantification in explants infected in the presence of SP. These results suggest that a sustained inflammatory response elicited by SP soon after coitus may promote HIV-1 transmission to the FGM. Nevertheless, ectocervical tissue explants did not support the replication of transmitted/founder HIV-1 molecular clones, regardless of SP treatment. Our system offers experimental and analytical advantages over traditional models of HIV-1 transmission for the study of SP immunoregulatory effect on the FGM, and may provide a useful platform to ultimately identify new determinants of HIV-1 infection at this site.
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spelling pubmed-54536132017-06-09 Seminal plasma induces inflammation and enhances HIV-1 replication in human cervical tissue explants Introini, Andrea Boström, Stéphanie Bradley, Frideborg Gibbs, Anna Glaessgen, Axel Tjernlund, Annelie Broliden, Kristina PLoS Pathog Research Article The most immediate and evident effect of mucosal exposure to semen in vivo is a local release of proinflammatory mediators accompanied by an influx of leukocytes into the female genital mucosa (FGM). The implication of such response in HIV-1 transmission has never been addressed due to limitations of currently available experimental models. Using human tissue explants from the uterine cervix, we developed a system of mucosal exposure to seminal plasma (SP) that supports HIV-1 replication. Treatment of ectocervical explants with SP resulted in the upregulation of inflammatory and growth factors, including IL-6, TNF, CCL5, CCL20, CXCL1, and CXCL8, and IL1A, CSF2, IL7, PTGS2, as evaluated by measuring protein levels in explant conditioned medium (ECM) and gene expression in tissue. SP treatment was also associated with increased recruitment of monocytes and neutrophils, as observed upon incubation of peripheral blood leukocytes with ECM in a transwell system. To evaluate the impact of the SP-mediated response on local susceptibility to HIV-1, we infected ectocervical explants with the CCR5-tropic variant HIV-1(BaL) either in the presence of SP, or after explant pre-incubation with SP. In both experimental settings SP enhanced virus replication as evaluated by HIV-1 p24(gag) released in explant culture medium over time, as well as by HIV-1 DNA quantification in explants infected in the presence of SP. These results suggest that a sustained inflammatory response elicited by SP soon after coitus may promote HIV-1 transmission to the FGM. Nevertheless, ectocervical tissue explants did not support the replication of transmitted/founder HIV-1 molecular clones, regardless of SP treatment. Our system offers experimental and analytical advantages over traditional models of HIV-1 transmission for the study of SP immunoregulatory effect on the FGM, and may provide a useful platform to ultimately identify new determinants of HIV-1 infection at this site. Public Library of Science 2017-05-19 /pmc/articles/PMC5453613/ /pubmed/28542587 http://dx.doi.org/10.1371/journal.ppat.1006402 Text en © 2017 Introini et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Introini, Andrea
Boström, Stéphanie
Bradley, Frideborg
Gibbs, Anna
Glaessgen, Axel
Tjernlund, Annelie
Broliden, Kristina
Seminal plasma induces inflammation and enhances HIV-1 replication in human cervical tissue explants
title Seminal plasma induces inflammation and enhances HIV-1 replication in human cervical tissue explants
title_full Seminal plasma induces inflammation and enhances HIV-1 replication in human cervical tissue explants
title_fullStr Seminal plasma induces inflammation and enhances HIV-1 replication in human cervical tissue explants
title_full_unstemmed Seminal plasma induces inflammation and enhances HIV-1 replication in human cervical tissue explants
title_short Seminal plasma induces inflammation and enhances HIV-1 replication in human cervical tissue explants
title_sort seminal plasma induces inflammation and enhances hiv-1 replication in human cervical tissue explants
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5453613/
https://www.ncbi.nlm.nih.gov/pubmed/28542587
http://dx.doi.org/10.1371/journal.ppat.1006402
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