The Progestin Medroxyprogesterone Acetate Affects HIV-1 Production in Human Lymphoid Tissue Explants in a Dose-Dependent and Glucocorticoid-like Fashion
The association between the use of the injectable contraceptive depot medroxyprogesterone acetate and HIV-1 susceptibility has been addressed mainly in respect to the changes occurring in the female genital mucosa and blood. However, one of the main sites of HIV-1 pathogenesis is lymphoid organs. To...
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oai:doaj.org-article:fbd963782d164fef985f0e60cd7ea2072021-11-25T19:14:23ZThe Progestin Medroxyprogesterone Acetate Affects HIV-1 Production in Human Lymphoid Tissue Explants in a Dose-Dependent and Glucocorticoid-like Fashion10.3390/v131123031999-4915https://doaj.org/article/fbd963782d164fef985f0e60cd7ea2072021-11-01T00:00:00Zhttps://www.mdpi.com/1999-4915/13/11/2303https://doaj.org/toc/1999-4915The association between the use of the injectable contraceptive depot medroxyprogesterone acetate and HIV-1 susceptibility has been addressed mainly in respect to the changes occurring in the female genital mucosa and blood. However, one of the main sites of HIV-1 pathogenesis is lymphoid organs. To investigate the immunoregulatory effect of medroxyprogesterone acetate (MPA) at this site, human tonsillar tissue explants were infected ex vivo with either a CCR5 (BaL) or CXCR4 (LAI) HIV-1 variant and the release of p24<sub>gag</sub> and cytokines was measured in culture supernatant. The response to MPA was compared with that elicited by treatment with progesterone (P4) and dexamethasone (DEX), which selectively binds the glucocorticoid receptor, in donor-matched explant cultures. MPA treatment reduced the replication of both tested HIV-1 strains as well as the production of the mediators of inflammation IL-1β, IL-17A and CCL5, but not CCL20, in a similar way to DEX, whereas P4 had no effect on HIV-1 replication. The magnitude of both MPA and DEX-mediated responses was proportional to the length of exposure and/or administered dose. Blockage of the progesterone and glucocorticoid receptors with mifepristone abolished all observed changes in HIV-1 and cytokine production, and was associated with increased IL-22 levels in HIV-infected explants. Our data indicate that elevated doses of MPA may affect the immune responses in lymphoid tissue in a glucocorticoid-like fashion with an immediate impact on local HIV-1 replication.Christophe VanpouilleGökçe GünaydınMattias JangardMario ClericiLeonid MargolisKristina BrolidenAndrea IntroiniMDPI AGarticlehormonal contraceptionsex hormonesprogesteroneDMPAglucocorticoidsHIV-1MicrobiologyQR1-502ENViruses, Vol 13, Iss 2303, p 2303 (2021) |
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DOAJ |
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DOAJ |
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hormonal contraception sex hormones progesterone DMPA glucocorticoids HIV-1 Microbiology QR1-502 |
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hormonal contraception sex hormones progesterone DMPA glucocorticoids HIV-1 Microbiology QR1-502 Christophe Vanpouille Gökçe Günaydın Mattias Jangard Mario Clerici Leonid Margolis Kristina Broliden Andrea Introini The Progestin Medroxyprogesterone Acetate Affects HIV-1 Production in Human Lymphoid Tissue Explants in a Dose-Dependent and Glucocorticoid-like Fashion |
| description |
The association between the use of the injectable contraceptive depot medroxyprogesterone acetate and HIV-1 susceptibility has been addressed mainly in respect to the changes occurring in the female genital mucosa and blood. However, one of the main sites of HIV-1 pathogenesis is lymphoid organs. To investigate the immunoregulatory effect of medroxyprogesterone acetate (MPA) at this site, human tonsillar tissue explants were infected ex vivo with either a CCR5 (BaL) or CXCR4 (LAI) HIV-1 variant and the release of p24<sub>gag</sub> and cytokines was measured in culture supernatant. The response to MPA was compared with that elicited by treatment with progesterone (P4) and dexamethasone (DEX), which selectively binds the glucocorticoid receptor, in donor-matched explant cultures. MPA treatment reduced the replication of both tested HIV-1 strains as well as the production of the mediators of inflammation IL-1β, IL-17A and CCL5, but not CCL20, in a similar way to DEX, whereas P4 had no effect on HIV-1 replication. The magnitude of both MPA and DEX-mediated responses was proportional to the length of exposure and/or administered dose. Blockage of the progesterone and glucocorticoid receptors with mifepristone abolished all observed changes in HIV-1 and cytokine production, and was associated with increased IL-22 levels in HIV-infected explants. Our data indicate that elevated doses of MPA may affect the immune responses in lymphoid tissue in a glucocorticoid-like fashion with an immediate impact on local HIV-1 replication. |
| format |
article |
| author |
Christophe Vanpouille Gökçe Günaydın Mattias Jangard Mario Clerici Leonid Margolis Kristina Broliden Andrea Introini |
| author_facet |
Christophe Vanpouille Gökçe Günaydın Mattias Jangard Mario Clerici Leonid Margolis Kristina Broliden Andrea Introini |
| author_sort |
Christophe Vanpouille |
| title |
The Progestin Medroxyprogesterone Acetate Affects HIV-1 Production in Human Lymphoid Tissue Explants in a Dose-Dependent and Glucocorticoid-like Fashion |
| title_short |
The Progestin Medroxyprogesterone Acetate Affects HIV-1 Production in Human Lymphoid Tissue Explants in a Dose-Dependent and Glucocorticoid-like Fashion |
| title_full |
The Progestin Medroxyprogesterone Acetate Affects HIV-1 Production in Human Lymphoid Tissue Explants in a Dose-Dependent and Glucocorticoid-like Fashion |
| title_fullStr |
The Progestin Medroxyprogesterone Acetate Affects HIV-1 Production in Human Lymphoid Tissue Explants in a Dose-Dependent and Glucocorticoid-like Fashion |
| title_full_unstemmed |
The Progestin Medroxyprogesterone Acetate Affects HIV-1 Production in Human Lymphoid Tissue Explants in a Dose-Dependent and Glucocorticoid-like Fashion |
| title_sort |
progestin medroxyprogesterone acetate affects hiv-1 production in human lymphoid tissue explants in a dose-dependent and glucocorticoid-like fashion |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/fbd963782d164fef985f0e60cd7ea207 |
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