Inflammation Of Female Genital Tract Research Articles

Antigen Presenting Cells Link the Female Genital Tract Microbiome to Mucosal Inflammation, With Hormonal Contraception as an Additional Modulator of Inflammatory Signatures.

The microbiome of the female genital tract (FGT) is closely linked to reproductive health outcomes. Diverse, anaerobe-dominated communities with low Lactobacillus abundance are associated with a number of adverse reproductive outcomes, such as preterm birth, cervical dysplasia, and sexually transmitted infections (STIs), including HIV. Vaginal dysbiosis is associated with local mucosal inflammation, which likely serves as a biological mediator of poor reproductive outcomes. Yet the precise mechanisms of this FGT inflammation remain unclear. Studies in humans have been complicated by confounding demographic, behavioral, and clinical variables. Specifically, hormonal contraception is associated both with changes in the vaginal microbiome and with mucosal inflammation. In this study, we examined the transcriptional landscape of cervical cell populations in a cohort of South African women with differing vaginal microbial community types. We also investigate effects of reproductive hormones on the transcriptional profiles of cervical cells, focusing on the contraceptive depot medroxyprogesterone acetate (DMPA), the most common form of contraception in sub-Saharan Africa. We found that antigen presenting cells (APCs) are key mediators of microbiome associated FGT inflammation. We also found that DMPA is associated with significant transcriptional changes across multiple cell lineages, with some shared and some distinct pathways compared to the inflammatory signature seen with dysbiosis. These results highlight the importance of an integrated, systems-level approach to understanding host-microbe interactions, with an appreciation for important variables, such as reproductive hormones, in the complex system of the FGT mucosa.

Inflammatory and antimicrobial properties differ between vaginal Lactobacillus isolates from South African women with non-optimal versus optimal microbiota

Female genital tract (FGT) inflammation increases HIV infection susceptibility. Non-optimal cervicovaginal microbiota, characterized by depletion of Lactobacillus species and increased bacterial diversity, is associated with increased FGT cytokine production. Lactobacillus species may protect against HIV partly by reducing FGT inflammation. We isolated 80 lactobacilli from South African women with non-optimal (Nugent 4–10; n = 18) and optimal microbiota (Nugent 0–3; n = 14). Cytokine production by vaginal epithelial cells in response to lactobacilli in the presence and absence of Gardnerella vaginalis was measured using Luminex. Adhesion to vaginal epithelial cells, pH, D/L-lactate production and lactate dehydrogenase relative abundance were assessed. Lactobacilli from women with non-optimal produced less lactic acid and induced greater inflammatory cytokine production than those from women with optimal microbiota, with IL-6, IL-8, IL-1α, IL-1β and MIP-1α/β production significantly elevated. Overall, lactobacilli suppressed IL-6 (adjusted p < 0.001) and IL-8 (adjusted p = 0.0170) responses to G. vaginalis. Cytokine responses to the lactobacilli were inversely associated with lactobacilli adhesion to epithelial cells and D-lactate dehydrogenase relative abundance. Thus, while cervicovaginal lactobacilli reduced the production of the majority of inflammatory cytokines in response to G. vaginalis, isolates from women with non-optimal microbiota were more inflammatory and produced less lactic acid than isolates from women with optimal microbiota.

Successful mast-cell-targeted treatment of chronic dyspareunia, vaginitis, and dysfunctional uterine bleeding

Dyspareunia, vaginitis and dysfunctional uterine bleeding (DUB) are common problems which, despite their polygenicity, commonly appear idiopathic and treatment-refractory. Mast cell (MC) activation syndrome (MCAS) is a newly-recognised, prevalent, chronic multisystem polymorbidity of general themes of inflammation ± allergic-type phenomena ± aberrant growth/development in assorted tissues. MCs produce significant quantities of heparin, too. As such, MCAS may underlie some cases of chronic dyspareunia, vaginitis or DUB. We report five such patients; all who responded well to MC-targeted treatment. We review aspects of MC biology and pathobiology of potential relevance to otherwise idiopathic persistent inflammatory or coagulopathic genital tract problems. Diagnostic testing for MCAS may be warranted in some patients with chronic dyspareunia, vaginitis or DUB (especially patients whose histories well fit the general profile of MCAS), and prospective therapeutic trials of MC-directed topical and/or systemic therapies may be warranted in such populations. Impact statement What is already known on this subject? Chronic, idiopathic, treatment-refractory female genital tract inflammation or bleeding are common problems for which mast cell (MC) disease, previously generally thought to consist of just rare cases of mastocytosis, and is seldom considered in the differential diagnosis. What do the results of this study add? The substantial prevalence of the newly recognised ‘mast cell activation syndrome’ (MCAS), featuring chronic inappropriate MC activation with little-to-no MC neoplasia, and its clinical presentation with chronic multisystem inflammation ± allergic-type phenomena ± aberrant growth/development in assorted tissues, raises the possibility that MCAS might underlie the aforementioned genital tract problems, especially in patients whose larger clinical presentations fit the MCAS profile. We report five example patients (among many more we have similarly treated) who enjoyed excellent responses to safe, inexpensive MC-targeted treatments, often given just intravaginally. What are the implications of these findings for clinical practice and/or further research? Our report identifies a potentially significant new MC-focused direction, of relevance to millions of affected women worldwide, for clinical treatment as well as for basic and clinical research, which historically has yielded major advancements disappointingly disproportionate to the scope of the affected population.

Female genital tract inflammation, HIV co-infection and persistent mucosal Human Papillomavirus (HPV) infections

BackgroundPersistent genital infections with high-risk HPV types increase risk of cervical disease and cancer. Since genital inflammation increases HIV acquisition risk and cancer progression, we evaluated whether HPV infection induces cytokine expression in the reproductive tract. MethodsGenital cytokines concentrations were measured in 93 HIV-infected and 72 uninfected women. HPV typing was done by Roche Linear array. Persistence and clearance of HPV were evaluated using longitudinal data. ResultsInfection with HPV did not influence genital cytokine concentrations. In contrast, HIV-infected women had higher IL-1α, IL-6, IL-8, IP-10, MCP-1 and G-CSF concentrations compared to HIV-uninfected women, and HPV-infections that were more prevalent, persistent and multi-type. ConclusionHPV did not influence inflammatory cytokine levels in the genital tract, although immune suppression may favor persistence.

Mucosal Proteomic Profiles Associated with Female Genital Tract Inflammation

AIDS Research and Human RetrovirusesVol. 30, No. S1 Mucosal Immune Activation and InflammationMucosal Proteomic Profiles Associated with Female Genital Tract InflammationKelly Arnold, Adam Burgener, Kenzie Birse, Laura Dunphy, Kamnoosh Shahabi, Max Abou, Jessie Kwatampora, Billy Nyanga, Joshua Kimani, Lenine Liebenberg, Lindi Masson, Salim S. Abdool Karim, Jo-Ann S. Passmore, Douglas A. Lauffenburger, Rupert Kaul, and Lyle R. McKinnonKelly ArnoldMIT, Boston, MA, United StatesSearch for more papers by this author, Adam BurgenerUniversity of Manitoba, Winnipeg, MB, CanadaSearch for more papers by this author, Kenzie BirseUniversity of Manitoba, Winnipeg, MB, CanadaSearch for more papers by this author, Laura DunphyMIT, Boston, MA, United StatesSearch for more papers by this author, Kamnoosh ShahabiUniversity of Toronto, Toronto, ON, CanadaSearch for more papers by this author, Max AbouPublic Health Agency of Canada, Winnipeg, MB, CanadaSearch for more papers by this author, Jessie KwatamporaUniversity of Nairobi, Nairobi, KenyaSearch for more papers by this author, Billy NyangaUniversity of Nairobi, Nairobi, KenyaSearch for more papers by this author, Joshua KimaniUniversity of Manitoba, Winnipeg, MB, CanadaSearch for more papers by this author, Lenine LiebenbergCAPRISA, Durban, South AfricaSearch for more papers by this author, Lindi MassonUniversity of Cape Town, Cape Town, South AfricaSearch for more papers by this author, Salim S. Abdool KarimCAPRISA, Durban, South AfricaSearch for more papers by this author, Jo-Ann S. PassmoreUniversity of Cape Town, Cape Town, South AfricaSearch for more papers by this author, Douglas A. LauffenburgerMIT, Boston, MA, United StatesSearch for more papers by this author, Rupert KaulUniversity of Toronto, Toronto, ON, CanadaSearch for more papers by this author, and Lyle R. McKinnonCAPRISA, Durban, South AfricaSearch for more papers by this authorPublished Online:30 Oct 2014https://doi.org/10.1089/aid.2014.5517.abstractAboutSectionsView articleView Full TextPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail View article"Mucosal Proteomic Profiles Associated with Female Genital Tract Inflammation." AIDS Research and Human Retroviruses, 30(S1), p. A235FiguresReferencesRelatedDetails Volume 30Issue S1Oct 2014 InformationCopyright 2014, Mary Ann Liebert, Inc.To cite this article:Kelly Arnold, Adam Burgener, Kenzie Birse, Laura Dunphy, Kamnoosh Shahabi, Max Abou, Jessie Kwatampora, Billy Nyanga, Joshua Kimani, Lenine Liebenberg, Lindi Masson, Salim S. Abdool Karim, Jo-Ann S. Passmore, Douglas A. Lauffenburger, Rupert Kaul, and Lyle R. McKinnon.Mucosal Proteomic Profiles Associated with Female Genital Tract Inflammation.AIDS Research and Human Retroviruses.Oct 2014.A235-A235.http://doi.org/10.1089/aid.2014.5517.abstractPublished in Volume: 30 Issue S1: October 30, 2014PDF download

Defining genital tract cytokine signatures of sexually transmitted infections and bacterial vaginosis in women at high risk of HIV infection: a cross-sectional study

ObjectivesSexually transmitted infections (STI) and bacterial vaginosis (BV) cause female genital tract inflammation. This inflammation, which is often present in the absence of symptoms, is associated with increased susceptibility to...

Male reproductive proteins and reproductive outcomes

Male reproductive proteins (MRPs), associated with sperm and semen, are the moieties responsible for carrying male genes into the next generation. Evolutionary biologists have focused on their capacity to control conception. Immunologists have shown that MRPs cause female genital tract inflammation as preparatory for embryo implantation and placentation. These observations argue that MRPs are critically important to reproductive success. Yet the impact of male reproductive proteins on obstetrical outcomes in women is largely unstudied. Epidemiologic and clinical observations suggest that shorter-duration exposure to MRPs prior to conception may elevate the risk for preeclampsia. A limited literature has also linked sexual behavior to bacterial vaginosis and preterm birth. We offer a clinical opinion that MRPs may have broad implications for successful reproduction, potentially involved in the composition of vaginal microflora, risks of preterm birth and preeclampsia, and success of assisted reproduction.