Research Article: Impact of chronic sexual abuse and depression on inflammation and wound healing in the female reproductive tract of HIV-uninfected and HIV-infected women

Date Published: June 12, 2018

Publisher: Public Library of Science

Author(s): Mimi Ghosh, Jason Daniels, Maria Pyra, Monika Juzumaite, Mariel Jais, Kerry Murphy, Tonya N. Taylor, Seble Kassaye, Lorie Benning, Mardge Cohen, Kathleen Weber, Soraya Seedat.

http://doi.org/10.1371/journal.pone.0198412

Abstract

Sexual violence is associated with increased risk of HIV acquisition/transmission in women. Forced sex can result in physical trauma to the reproductive tract as well as severe psychological distress. However, immuno-biological mechanisms linking sexual violence and HIV susceptibility are incompletely understood. Using the Women’s Interagency HIV Study repository, a total of 77 women were selected to form 4 groups, stratified by HIV serostatus, in the following categories: 1) no sexual abuse history and low depressive symptom score (below clinically significant cut-off, scores <16) (Control); 2) no sexual abuse history but high depressive symptom score, ≥16 (Depression); 3) chronic sexual abuse exposure and low depressive symptom score (Abuse); 4) chronic sexual abuse exposure and high depressive symptom score (Abuse+Depression). Inflammation-associated cytokines/chemokines/proteases (TNF-α, IL-6, IL-1α, IL-1β, TGF-β MIP-3α, IP-10, MCP-1, Cathepsin B), anti-inflammatory/anti-HIV mediators (Secretory leukocyte protease inhibitor (SLPI), Elafin, beta defensin 2 (HBD2), alpha defensins (HNP 1–3), Thrombospondin (TSP-1), Serpin A1, A5, Cystatin A, B), and wound-healing mediators (Gro-α, VEGF, PDGF, EGF, FGF, IGF), were measured in cervical-vaginal lavage (CVL) using ELISA. Linear regression was used to model association of biomarkers with depression and abuse as predictor variables; the interaction between depression and abuse was also tested. Anti-HIV activity in CVL was tested using TZM-bl indicator cell line. In HIV-uninfected women, median levels of IL-6 (p = 0.04), IL-1α (p<0.01), TGF-β (p = 0.01), IP-10 (p = <0.01), PDGF (p<0.01) and FGF (p<0.01), differed significantly between groups. Specifically, an association was found between chronic sexual abuse and increased IL-1α (p<0.01), MIP-3α (p = 0.04), IP-10 (p<0.01), Serpin B1 (p = 0.01), FGF (p = 0.04) and decreased TGF-β (p<0.01), MCP-1 (p = 0.02), PDGF (p<0.01). Further, there was evidence of significant interactions between chronic sexual abuse and current depression for IL-1α, IP-10, Serpin A1, Cystatin B, and FGF. In HIV-infected women, median levels of TNF-α (p<0.01), IL-6 (p = 0.05), MIP-3α (p<0.01), and MCP-1 (p = 0.01), differed significantly between groups. Specifically, an association was found between chronic sexual abuse and increased MCP-1 (p = 0.03), Gro-α (p = 0.01) and decreased TNF-α (p<0.01), IL-1α (p = 0.02), MIP-3α (p<0.01) and Cathepsin B (p = 0.03). Current depressive symptoms were associated with significantly decreased MIP-3α (p<0.01). There was evidence of significant interactions between chronic sexual abuse and current depression for MCP-1 and FGF. No significant differences were observed in anti-HIV activity among all eight groups. Heat-map analyses revealed distinct immune network patterns, particularly in the Abuse groups for both HIV-infected and uninfected women. Our data indicates a complex relationship between chronic sexual abuse exposure, depressive symptoms, and FRT immune mediators that are also affected by HIV status. Association of chronic sexual abuse with increase in inflammation-associated cytokine/chemokine expression, along with impaired wound-healing associated growth-factors can create a microenvironment that can facilitate HIV infection. Evaluation of longitudinal changes in exposures and biomarkers are needed to untangle the immuno-biological mechanisms that may put women who endure life-long sexual abuse at increased risk for HIV.

Partial Text

Violence and HIV/AIDS form a tragic feedback loop that disproportionately affects women worldwide [1]. In the United States alone, partner violence and sexual assault are the first and sixth leading causes of injury in women, respectively [2],[3]. Globally, it is estimated that about 1 in 3 women experience physical violence in their lifetimes, most of which is committed by an intimate partner [4]. Women are also more likely to be affected by the HIV/AIDS epidemic. As of 2015, 51% of all HIV infections were in women, with the greatest burden (60%) among young adults [5]. Violence against women has been significantly associated with increased risk of HIV acquisition/transmission [1],[6].

Our data indicate that exposure to chronic sexual abuse and current depressive symptoms can be associated with immune alterations which can include a state of inflammation, immune activation, and modified wound healing pathways within the FRT, thereby increasing risk of HIV acquisition/transmission. These findings have clinical implications in HIV prevention efforts, as therapies that abate inflammation and immune activation (such as using anti-inflammatory drugs, [52]) and modulate wound healing [53], could be applied to reduce risks of HIV infection in women who have histories of abuse and depression. Fig 4 shows a schematic of our hypothesis and major findings.

 

Source:

http://doi.org/10.1371/journal.pone.0198412

 

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