Role of semen in modulating the female genital tract microenvironment--implications for HIV transmission (original) (raw)
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Viral Immunology, 2014
While the main reproduction aim of semen is the transport of spermatozoa to the female genital tract, seminal plasma is a complex fluid that also carries a broad array of immunologically active molecules. Seminal plasma has been shown to contain a diverse array of anti-inflammatory and pro-inflammatory soluble mediators that regulate immune responses within the female reproductive tract than can facilitate fertilization. Since the natural inflammatory response to semen deposition in the female genital tract may result in recruitment of activated HIV target cells into the female genital mucosa, we discuss the constituents of semen that may increase the risk for HIV infection in women.
Frontiers in Immunology
Genital inflammatory cytokine responses increase HIV risk. Since male partner semen is a complex mixture of immune-modulatory prostaglandins and cytokines, we hypothesized that exposure to semen may influence genital inflammation in women. Here, we investigated cytokine response kinetics of cervical cells following stimulation with seminal plasma from HIV-negative and HIV-positive men characterized as having low or high concentrations of inflammatory cytokines. Irrespective of the HIV status or semen cytokine profile, in vitro stimulation of cervical cells with seminal plasma resulted in significantly elevated concentrations of secreted IL-6, IL-8, TNF-β, MCP-1, GM-CSF, and VEGF within 8 h of stimulation, which tended to decline by 24 h, although this was only significant for TNF-β. Consistent with this, cervical cells responded to seminal plasma with increases in IL-8 and IL-1β mRNA expression of 10-fold. These findings suggest that the impact of semen on local female genital cytokines is likely transient. Although these findings suggest that the impact of semen on local female genital cytokines may not be sustained long-term, this heightened genital inflammation may have implications for HIV risk in women.
Recent Semen Exposure Impacts the Cytokine Response and Bacterial Vaginosis in Women
Frontiers in Immunology, 2021
BackgroundThe presence of semen in the vagina from unprotected sex may influence the immune and microbial environment of the female genital tract. Inflammatory cytokine concentrations and BV-associated bacteria in female genital secretions may influence HIV risk, although the effect of recent sexual intercourse on incident BV and the cytokine milieu of cervicovaginal secretions has rarely been measured in previous studies. Here, we investigated the extent to which partner semen impacts the cytokine response and incident BV.MethodsAt baseline, we assessed the recency of semen exposure in menstrual cup supernatants by quantifying prostate specific antigen (PSA) levels using ELISA in 248 HIV-uninfected women at high risk for HIV infection. Luminex was used to measure 48 cytokines in menstrual cup supernatants and vaginal swabs to diagnose BV by Nugent score. Point-of-care screening for Chlamydia trachomatis and Neisseria gonorrhoeae was conducted using GeneXpert while OSOM was used for...
Sperm can act as vectors for HIV‐1 transmission into vaginal and cervical epithelial cells
American Journal of Reproductive Immunology, 2019
Sperm are the major cells in semen. Human sperm possess a number of HIV-1 gp120 binding ligands including sulfogalactosylglycerolipid (SGG). However, the mechanisms of how sperm capture HIV-1 onto their surface are unclear. Furthermore, the ability of sperm to deliver HIV-1 to vaginal/cervical epithelial cells lining the lower female reproductive tract, as a first step in HIV-1 transmission, needs to be established. Method of study: Sperm from healthy donors were incubated with dual-tropic HIV-1 CS204 (clinical isolate) and virus capture was determined by p24 antigen ELISA. The involvement of SGG in HIV-1 capture was assessed by determining K d values of HIV-1 gp120-SGG binding as well as computational docking of SGG to the gp120 V3 loop. The ability of spermassociated HIV-1 to infect peripheral blood mononuclear cells (PBMCs) and TZM-bl indicator cells was determined. Lastly, infection of vaginal (Vk2/E6E7), ectocervical (Ect1/E6E7) and endocervical (End1/E6E7) epithelial cells mediated by HIV-1-associated sperm was evaluated. Results: Sperm were able to capture HIV-1 in a dose-dependent manner and the capture reached a maximum within 5 min. Captured HIV-1, however, could be removed from sperm by Percoll gradient centrifugation. Affinity of gp120 for SGG was substantial, implicating sperm SGG in HIV-1 capture. Sperm-associated HIV-1 could productively infect PBMCs and TZM-bl cells, and was capable of being transmitted into vaginal/cervical epithelial cells.
Human Vaccines & Immunotherapeutics
HIV-1 sexual transmission occurs mostly through contaminated semen, which is a complex mixture of soluble factors with immunoregulatory functions and cells. It is well established that semen cells from HIV-1-infected men are able to produce the virus and that are harnessed to efficiently interact with mucosal barriers exposed during sexual intercourse. Several cofactors contribute to semen infectivity and may enhance the risk of HIV-1 transmission to a partner by increasing local HIV-1 replication in the male genital tract, thereby increasing the number of HIV-1-infected cells and the local HIV-1 shedding in semen. The introduction of combination antiretroviral therapy has improved the life expectancy of HIV-1 infected individuals; however, there is evidence that systemic viral suppression does not always reflect full viral suppression in the seminal compartment. This review focus on the role semen leukocytes play in HIV-1 transmission and discusses implications of the increased resistance of cell-mediated transmission to immune-based prevention strategies.
2018
My sincere gratitude goes to my supervisor and mentor Dr Sinaye Ngcapu, thank you for taking a chance on me and trusting me with this project. Thank you so much for your encouragement and support on days when I felt discouraged. Thank you for pushing me to complete this work and your excellent guidance in the write up. You have granted me the opportunity to learn and grow as an aspiring young scientist. I would also like to thank my co-supervisor Dr Cheryl Baxter for reviewing my work and valuable suggestions. I'd also like to thank the following individuals for their amazing contributions to this thesis: Andile
Cytometry, 1996
The purpose of this study was to determine the types and distribution of immune subsets present in semen from human immunodeficiency virus (HIV)-infected (HIV+) individuals and to compare these values with those measures in semen from HIV-negative (HIV-) individuals. To accomplish this, a direct three-color monoclonal antibody labeling technique was employed to identify immune cells in fresh ejaculates. Once labeled, the percent of each immune subset present in the ejaculate was determined by flow cytometric analysis. The percent of CD3+ cells present in the semen of the HIV+ group showed no significant difference when compared with semen from the HIV-group. Analysis of the CD4+ subset yielded a significantly lower percent in the HIV+ group than in the HIV-group. The analysis of the CD8+ subset yielded a higher percent of cells present in semen from HIV+ individuals. The CD8 higher value along with lower CD4 value results in a lower CD4/CD8 ratio in the HIV+ group. Further subset studies showed that the percent of cells expressing naive (CD4+CD45RA+) and memory (CD4+CD45RO+) markers was lower in the HIV+ group. This study provides additional data supporting the utility of flow cytometry and monoclonal antibodies to immunophenotypic cells present in semen ejaculates. It is also the first reported application of the technique to a disease-based model and may be useful to better understand issues of mucosal immunity and transmission of sexually transmitted diseases such as HIV. D 1996 Wiley-Liss, Inc.