Reduced Levels and Bioactivity of Endogenous Protease Cathepsin D in Genital Tract Secretions of Postmenopausal Women

Jais, Mariel; Younes, Naji; Chapman, Stacey; Cu‐Uvin, Susan; Ghosh, Mimi

doi:10.1089/aid.2016.0240

Cited by 3 publications

(2 citation statements)

References 7 publications

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“…We and others have previously shown lower levels of several critical immune mediators in CVL samples from healthy, HIV-negative postmenopausal women compared with premenopausal women. [16][17][18] Our current data extend these findings and confirm similar patterns for most mediators that we tested in HIV-positive women who have not been on antiretroviral therapy at least for the past 6 months. Two of these immune mediators, SLPI and HBD2, have in vitro anti-HIV functions.…”

Section: Discussionsupporting

confidence: 86%

“…14,16 We and others have previously shown reduced levels of soluble immune mediators in genital secretions among postmenopausal women compared with premenopausal women. [16][17][18] As many of these immune mediators are reported to be regulated by estradiol, 19,20 reduction following menopause is not surprising. However, it is less clear as to what extent this reduction affects overall functional immunity in the FGT.…”

Section: Introductionmentioning

confidence: 99%

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Dysregulation in Genital Tract Soluble Immune Mediators in Postmenopausal Women Is Distinct by HIV Status

Ghosh

Jais

Delisle

et al. 2019

AIDS Research and Human Retroviruses

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A rise in new HIV diagnoses among older adults is characterized by poor prognosis and reduced survival times. Although heterosexual transmission remains the main route of infection in women, little is known regarding immune functions in the genital tract of postmenopausal women, especially those who are HIV positive. Furthermore, effects of hormone replacement therapy (HRT) on the genital tract immune system are unclear. Using the Women's Interagency HIV Study repository, we obtained cervical-vaginal lavage (CVL) samples from premenopausal and postmenopausal HIV-positive and HIV-negative women, some of whom were on HRT. Samples were assayed for interleukin (IL)-6, IL-8, tumor necrosis factor (TNF)-a, secretory leukocyte protease inhibitor (SLPI), Elafin, human beta defensin-2 (HBD2), and macrophage inflammatory protein (MIP)-3a using ELISA. Anti-HIV activity in CVL was measured using TZM-bl indicator cells. Among HIV-positive women, the plasma viral load was significantly higher and CD4 count was significantly lower in postmenopausal compared with premenopausal women. Postmenopausal women, irrespective of HIV status, had significantly lower levels of HBD2 compared with premenopausal women. Among the HIV-negative individuals, postmenopausal women had significantly lower levels of MIP-3a, IL-6, and SLPI compared with premenopausal women. In contrast, HIV-positive postmenopausal women had significantly higher levels of TNF-a compared with HIV-positive premenopausal women. In most cases, HRT groups resembled the postmenopausal groups. No significant differences in anti-HIV activity by menopausal or by HIV status were noted. Our findings indicate that the female genital tract immune microenvironment is distinct by menopausal status and HIV status. Further studies are needed to assess the risk of HIV acquisition/transmission in this population.

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Section: Discussionsupporting

confidence: 86%

Section: Introductionmentioning

confidence: 99%

Dysregulation in Genital Tract Soluble Immune Mediators in Postmenopausal Women Is Distinct by HIV Status

Ghosh

Jais

Delisle

et al. 2019

AIDS Research and Human Retroviruses

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HIV Pathogenesis in the Human Female Reproductive Tract

2021

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Changes in concentrations of cervicovaginal immune mediators across the menstrual cycle: a systematic review and meta-analysis of individual patient data

Hughes

Levy²,

Katz³

et al. 2022

BMC Med

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Background Hormonal changes during the menstrual cycle play a key role in shaping immunity in the cervicovaginal tract. Cervicovaginal fluid contains cytokines, chemokines, immunoglobulins, and other immune mediators. Many studies have shown that the concentrations of these immune mediators change throughout the menstrual cycle, but the studies have often shown inconsistent results. Our understanding of immunological correlates of the menstrual cycle remains limited and could be improved by meta-analysis of the available evidence. Methods We performed a systematic review and meta-analysis of cervicovaginal immune mediator concentrations throughout the menstrual cycle using individual participant data. Study eligibility included strict definitions of the cycle phase (by progesterone or days since the last menstrual period) and no use of hormonal contraception or intrauterine devices. We performed random-effects meta-analyses using inverse-variance pooling to estimate concentration differences between the follicular and luteal phases. In addition, we performed a new laboratory study, measuring select immune mediators in cervicovaginal lavage samples. Results We screened 1570 abstracts and identified 71 eligible studies. We analyzed data from 31 studies, encompassing 39,589 concentration measurements of 77 immune mediators made on 2112 samples from 871 participants. Meta-analyses were performed on 53 immune mediators. Antibodies, CC-type chemokines, MMPs, IL-6, IL-16, IL-1RA, G-CSF, GNLY, and ICAM1 were lower in the luteal phase than the follicular phase. Only IL-1α, HBD-2, and HBD-3 were elevated in the luteal phase. There was minimal change between the phases for CXCL8, 9, and 10, interferons, TNF, SLPI, elafin, lysozyme, lactoferrin, and interleukins 1β, 2, 10, 12, 13, and 17A. The GRADE strength of evidence was moderate to high for all immune mediators listed here. Conclusions Despite the variability of cervicovaginal immune mediator measurements, our meta-analyses show clear and consistent changes during the menstrual cycle. Many immune mediators were lower in the luteal phase, including chemokines, antibodies, matrix metalloproteinases, and several interleukins. Only interleukin-1α and beta-defensins were higher in the luteal phase. These cyclical differences may have consequences for immunity, susceptibility to infection, and fertility. Our study emphasizes the need to control for the effect of the menstrual cycle on immune mediators in future studies.

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Reduced Levels and Bioactivity of Endogenous Protease Cathepsin D in Genital Tract Secretions of Postmenopausal Women

Cited by 3 publications

References 7 publications

Dysregulation in Genital Tract Soluble Immune Mediators in Postmenopausal Women Is Distinct by HIV Status

Dysregulation in Genital Tract Soluble Immune Mediators in Postmenopausal Women Is Distinct by HIV Status

HIV Pathogenesis in the Human Female Reproductive Tract

Changes in concentrations of cervicovaginal immune mediators across the menstrual cycle: a systematic review and meta-analysis of individual patient data

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