The Contribution of Cervicovaginal Infections to the Immunomodulatory Effects of Hormonal Contraception

ABSTRACT Particular types of hormonal contraceptives (HCs) and genital tract infections have been independently associated with risk of HIV-1 acquisition. We examined whether immunity in women using injectable depot medroxyprogesterone acetate (DMPA), combined oral contraceptives (COC), or no HCs di...

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Autores principales:	Raina N. Fichorova, Pai-Lien Chen, Charles S. Morrison, Gustavo F. Doncel, Kevin Mendonca, Cynthia Kwok, Tsungai Chipato, Robert Salata, Christine Mauck
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2015
Materias:	Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/319867ed50f64d4bba24e692fc874259
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spelling	oai:doaj.org-article:319867ed50f64d4bba24e692fc8742592021-11-15T15:41:30ZThe Contribution of Cervicovaginal Infections to the Immunomodulatory Effects of Hormonal Contraception10.1128/mBio.00221-152150-7511https://doaj.org/article/319867ed50f64d4bba24e692fc8742592015-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00221-15https://doaj.org/toc/2150-7511ABSTRACT Particular types of hormonal contraceptives (HCs) and genital tract infections have been independently associated with risk of HIV-1 acquisition. We examined whether immunity in women using injectable depot medroxyprogesterone acetate (DMPA), combined oral contraceptives (COC), or no HCs differs by the presence of cervicovaginal infections. Immune mediators were quantified in cervical swabs from 832 HIV-uninfected reproductive-age Ugandans and Zimbabweans. Bacterial infections and HIV were diagnosed by PCR, genital herpes serostatus by enzyme-linked immunosorbent assay (ELISA), altered microflora by Nugent score, and Trichomonas vaginalis and Candida albicans infection by wet mount. Generalized linear models utilizing Box-Cox-Power transformation examined associations between levels of mediators, infection status, and HCs. In no-HC users, T. vaginalis was associated with broadest spectrum of aberrant immunity (higher interleukin 1β [IL-1β], IL-8, macrophage inflammatory protein 3α [MIP-3α], β-defensin 2 [BD2], and IL-1 receptor antigen [IL-1RA]). In women with a normal Nugent score and no genital infection, compared to the no-HC group, COC users showed higher levels of IL-1β, IL-6, IL-8, and IL-1RA, while DMPA users showed higher levels of RANTES and lower levels of BD2, both associated with HIV seroconversion. These effects of COC were blunted in the presence of gonorrhea, chlamydia, trichomoniasis, candidiasis, and an abnormal Nugent score; however, RANTES was increased among COC users with herpes, chlamydia, and abnormal Nugent scores. The effect of DMPA was exacerbated by lower levels of IL-1RA in gonorrhea, chlamydia, or herpes, SLPI in gonorrhea, and IL-1β, MIP-3α, and IL-1RA/IL1β ratio in trichomoniasis. Thus, the effects of HC on cervical immunity depend on the genital tract microenvironment, and a weakened mucosal barrier against HIV may be a combined resultant of genital tract infections and HC use. IMPORTANCE In this article, we show that in young reproductive-age women most vulnerable to HIV, hormonal contraceptives are associated with altered cervical immunity in a manner dependent on the presence of genital tract infections. Through altered immunity, hormones may predispose women to bacterial and viral pathogens; conversely, a preexisting specific infection or disturbed vaginal microbiota may suppress the immune activation by levonorgestrel or exacerbate the suppressed immunity by DMPA, thus increasing HIV risk by their cumulative action. Clinical studies assessing the effects of contraception on HIV susceptibility and mucosal immunity may generate disparate results in populations that differ by microbiota background or prevalence of undiagnosed genital tract infections. A high prevalence of asymptomatic infections among HC users that remain undiagnosed and untreated raises even more concerns in light of their combined effects on biomarkers of HIV risk. The molecular mechanisms of the vaginal microbiome's simultaneous interactions with hormones and HIV remain to be elucidated.Raina N. FichorovaPai-Lien ChenCharles S. MorrisonGustavo F. DoncelKevin MendoncaCynthia KwokTsungai ChipatoRobert SalataChristine MauckAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 5 (2015)
institution	DOAJ
collection	DOAJ
language	EN
topic	Microbiology QR1-502
spellingShingle	Microbiology QR1-502 Raina N. Fichorova Pai-Lien Chen Charles S. Morrison Gustavo F. Doncel Kevin Mendonca Cynthia Kwok Tsungai Chipato Robert Salata Christine Mauck The Contribution of Cervicovaginal Infections to the Immunomodulatory Effects of Hormonal Contraception
description	ABSTRACT Particular types of hormonal contraceptives (HCs) and genital tract infections have been independently associated with risk of HIV-1 acquisition. We examined whether immunity in women using injectable depot medroxyprogesterone acetate (DMPA), combined oral contraceptives (COC), or no HCs differs by the presence of cervicovaginal infections. Immune mediators were quantified in cervical swabs from 832 HIV-uninfected reproductive-age Ugandans and Zimbabweans. Bacterial infections and HIV were diagnosed by PCR, genital herpes serostatus by enzyme-linked immunosorbent assay (ELISA), altered microflora by Nugent score, and Trichomonas vaginalis and Candida albicans infection by wet mount. Generalized linear models utilizing Box-Cox-Power transformation examined associations between levels of mediators, infection status, and HCs. In no-HC users, T. vaginalis was associated with broadest spectrum of aberrant immunity (higher interleukin 1β [IL-1β], IL-8, macrophage inflammatory protein 3α [MIP-3α], β-defensin 2 [BD2], and IL-1 receptor antigen [IL-1RA]). In women with a normal Nugent score and no genital infection, compared to the no-HC group, COC users showed higher levels of IL-1β, IL-6, IL-8, and IL-1RA, while DMPA users showed higher levels of RANTES and lower levels of BD2, both associated with HIV seroconversion. These effects of COC were blunted in the presence of gonorrhea, chlamydia, trichomoniasis, candidiasis, and an abnormal Nugent score; however, RANTES was increased among COC users with herpes, chlamydia, and abnormal Nugent scores. The effect of DMPA was exacerbated by lower levels of IL-1RA in gonorrhea, chlamydia, or herpes, SLPI in gonorrhea, and IL-1β, MIP-3α, and IL-1RA/IL1β ratio in trichomoniasis. Thus, the effects of HC on cervical immunity depend on the genital tract microenvironment, and a weakened mucosal barrier against HIV may be a combined resultant of genital tract infections and HC use. IMPORTANCE In this article, we show that in young reproductive-age women most vulnerable to HIV, hormonal contraceptives are associated with altered cervical immunity in a manner dependent on the presence of genital tract infections. Through altered immunity, hormones may predispose women to bacterial and viral pathogens; conversely, a preexisting specific infection or disturbed vaginal microbiota may suppress the immune activation by levonorgestrel or exacerbate the suppressed immunity by DMPA, thus increasing HIV risk by their cumulative action. Clinical studies assessing the effects of contraception on HIV susceptibility and mucosal immunity may generate disparate results in populations that differ by microbiota background or prevalence of undiagnosed genital tract infections. A high prevalence of asymptomatic infections among HC users that remain undiagnosed and untreated raises even more concerns in light of their combined effects on biomarkers of HIV risk. The molecular mechanisms of the vaginal microbiome's simultaneous interactions with hormones and HIV remain to be elucidated.
format	article
author	Raina N. Fichorova Pai-Lien Chen Charles S. Morrison Gustavo F. Doncel Kevin Mendonca Cynthia Kwok Tsungai Chipato Robert Salata Christine Mauck
author_facet	Raina N. Fichorova Pai-Lien Chen Charles S. Morrison Gustavo F. Doncel Kevin Mendonca Cynthia Kwok Tsungai Chipato Robert Salata Christine Mauck
author_sort	Raina N. Fichorova
title	The Contribution of Cervicovaginal Infections to the Immunomodulatory Effects of Hormonal Contraception
title_short	The Contribution of Cervicovaginal Infections to the Immunomodulatory Effects of Hormonal Contraception
title_full	The Contribution of Cervicovaginal Infections to the Immunomodulatory Effects of Hormonal Contraception
title_fullStr	The Contribution of Cervicovaginal Infections to the Immunomodulatory Effects of Hormonal Contraception
title_full_unstemmed	The Contribution of Cervicovaginal Infections to the Immunomodulatory Effects of Hormonal Contraception
title_sort	contribution of cervicovaginal infections to the immunomodulatory effects of hormonal contraception
publisher	American Society for Microbiology
publishDate	2015
url	https://doaj.org/article/319867ed50f64d4bba24e692fc874259
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The Contribution of Cervicovaginal Infections to the Immunomodulatory Effects of Hormonal Contraception

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