American Journal of Reproductive Immunology最新文献

{"title":"Assessing the Impact of Female Genital Mutilation/Cutting on Genital Inflammation and Microbiota Among Kenyan Female Sex Workers.","authors":"James Pollock, Rachel Liu, Elizabeth Rwenji, Evelyne Orobi, Suji Udayakumar, Sanja Huibner, Mary Kung'u, Rhoda Kabuti, Hellen Babu, Erastus Irungu, Pauline Ngurukiri, Peter Muthoga, Wendy Adhiambo, Helen A Weiss, Janet Seeley, Tanya Abramsky, Joshua Kimani, Tara S Beattie, Rupert Kaul","doi":"10.1111/aji.70250","DOIUrl":"10.1111/aji.70250","url":null,"abstract":"<p><strong>Problem: </strong>Female genital mutilation/cutting (FGM/C) is harmful to physical, mental, and reproductive health, though the effect of this practice on a woman's HIV susceptibility is poorly understood. Despite the known associations of FGM/C with short-term vaginal epithelial damage, neither genital inflammation nor the genital microbiome have been explored in women who have undergone FGM/C. In this study we compare the genital immune milieu and microbiome among female sex workers (FSWs) by FGM/C status, hypothesizing that these biological factors are dysregulated in women who have undergone FGM/C, heightening their risk of HIV acquisition.</p><p><strong>Method of study: </strong>1003 FSWs in Nairobi, Kenya, were enrolled in the Maisha Fiti study and visited a study clinic up to three times from June 2019 to March 2021. Participants self-reported any previous exposure to FGM/C as well as other relevant sociodemographic factors. Levels of proinflammatory cytokines and soluble E-cadherin (sE-cad), a biomarker of epithelial barrier disruption, were measured by multiplex immunoassay using self-collected cervicovaginal secretion samples provided by HIV-uninfected participants. Genital inflammation was defined using a composite score of inflammatory cytokines previously associated with HIV acquisition. The presence of inflammation was compared longitudinally between groups using mixed models to control for potential confounders including age, bacterial vaginosis (BV) status as defined by Nugent score, and others. Vaginal bacterial abundance, Shannon diversity, and total levels of key vaginal bacteria were measured by qPCR and compared by FGM/C status in an exploratory analysis.</p><p><strong>Results: </strong>44 of 1003 (4%) participants had undergone Type I or II FGM/C. These participants were older (p < 0.001) and more likely to test positive for herpes simplex virus-2 (HSV-2; p = 0.04), and less likely to have completed primary education (p = 0.03). Among HIV-uninfected participants, there was no evidence that genital inflammation was associated with FGM/C status after controlling for potential confounders (aOR = 0.70; 95% CI: 0.31-1.59; p = 0.40). There was no evidence of a difference in BV prevalence (p > 0.99), total bacterial abundance (p = 0.96), or Shannon diversity (p = 0.15) by FGM/C status.</p><p><strong>Conclusions: </strong>Type I or II FGM/C was not associated with genital inflammation or microbial dysregulation in the long-term among HIV-negative FSWs in this cohort. This may be due to the duration elapsed since FGM/C occurred or the lowered mucosal immune activation previously observed in FSWs.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 5","pages":"e70250"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13138364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809631","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anaerobe-Driven Inflammation and Epithelial Barrier Disruption in Genital HIV Acquisition.","authors":"Shirley Constable, Yasamin Minazadeh, Lane B Buchanan, Henryroger Ssemunywa, Ronald M Galiwango, Rupert Kaul, Jessica L Prodger","doi":"10.1111/aji.70251","DOIUrl":"10.1111/aji.70251","url":null,"abstract":"<p><strong>Background: </strong>Genital microbiome dysbiosis is an important risk factor for the sexual acquisition of human immunodeficiency virus (HIV) in both the male and female genital tracts. The vaginal, penile and urethral mucosae are distinct microenvironments with characteristic microbiome compositions. However, all three sites can be colonised by a group of strictly anaerobic bacteria that are strongly associated with mucosal inflammation and HIV risk. Our understanding of the relationship between genital anaerobes and HIV acquisition has largely focused on mucosal target cell density and activation. Yet, genital anaerobes disrupt epithelial barrier integrity, a crucial component of mucosal defence.</p><p><strong>Objective: </strong>To comprehensively evaluate the influence of genital anaerobes on epithelial barrier integrity in the context of HIV acquisition, across the penile, vaginal, and urethral mucosae.</p><p><strong>Results: </strong>Within the vaginal microbiome, anaerobes have been studied extensively in the context of bacterial vaginosis and several mechanisms of mucosal barrier disruption, including mucus degradation, epithelial cell damage and junction protein cleavage, have been identified and linked to HIV risk. The effects of these same bacteria are less defined in the context of the penile and urethral epithelia, despite their prevalence and association with HIV acquisition.</p><p><strong>Conclusions: </strong>Further investigation of genital anaerobe-mediated barrier disruption in both sexes is needed to elucidate shared and site-specific mechanisms influencing HIV transmission. This knowledge is essential to understanding HIV risk and developing effective prevention strategies.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 5","pages":"e70251"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148465/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tenofovir, Interferon Pathways, and Mucosal Immunity: Implications for People Living With HIV.","authors":"Florian Hladik, Sean M Hughes, Claire N Levy, Rachel L Creighton, Romel Mackelprang, Germán G Gornalusse","doi":"10.1111/aji.70255","DOIUrl":"10.1111/aji.70255","url":null,"abstract":"<p><strong>Background: </strong>Antiretroviral therapy (ART) suppresses HIV replication and protects people living with HIV (PLWH) from progressing to AIDS. However, despite ART, many PLWH experience chronic immune activation, which contributes to premature aging and non-AIDS-related comorbidities. One reason for this chronic immune activation (CIA) is HIV and its reservoir. There is, however, accumulating evidence for an unexpected contributor: the nucleoside/nucleotide reverse transcriptase inhibitor (NRTI) class of drugs, particularly tenofovir, which can independently induce interferon (IFN) signaling in mucosal tissues. This CIA-driving effect of tenofovir and other NRTIs warrants further study, as these therapies are taken lifelong and PLWH suffer disproportionately from inflammation-related comorbidities.</p><p><strong>Objective: </strong>This review synthesizes evidence demonstrating that tenofovir contributes to CIA across multiple mucosal compartments (rectum, duodenum, and vagina) in both HIV-uninfected and infected individuals. We detail the known mechanisms that likely underlie NRTI-induced CIA: (1) Suppression of interleukin 10 (IL-10), and induction of interleukin 12 (IL-12) and interferon-stimulated genes (ISGs), through inhibition of the protein kinase AKT, and (2) interferon response-enhancing interactions with endogenous retroelements. Tenofovir also increases the number of specialized ISG^high epithelial cells in the gut. We further discuss the hypothesis that the chronic interferon signaling driven by NRTIs exacerbates HIV reservoir persistence and T-cell exhaustion. Finally, we propose emerging therapeutic strategies, including NRTI-sparing antiretroviral regimens and targeted immunomodulatory treatments, to reduce CIA and improve clinical outcomes for PLWH.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 5","pages":"e70255"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13177280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147866241","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Approaches for Investigating Host Responses to HIV Infection in Ex Vivo Human Genital Tissues.","authors":"Mathias Franzén Boger, Vilde Kaldhusdal, Kristina Broliden","doi":"10.1111/aji.70240","DOIUrl":"10.1111/aji.70240","url":null,"abstract":"<p><p>Understanding local immune responses and the structural integrity of the genital mucosal barrier is essential for advancing knowledge of both susceptibility to sexual HIV transmission and the pathogenesis of chronic HIV infection. This review highlights innovative methodologies for investigating host responses to HIV infection using ex vivo human genital tissues. Recent advances in spatial transcriptomics and multiplex imaging enable high-resolution analysis of tissue architecture, immune cell distribution, and gene expression within mucosal environments. These technologies reveal spatially heterogeneous immune responses as well as epithelial and submucosal structural alterations associated with increased HIV susceptibility and chronic infection. Computational workflows tailored to genital tissue morphology enhance reproducibility and support the integration of transcriptomic and imaging data. Despite current limitations, such as resolution constraints and high costs, ongoing improvements in spatial transcriptomics and bioimaging platforms promise deeper insights into mucosal barrier function and HIV pathogenesis. Characterizing tissue-specific immune dynamics through these approaches may guide the development of targeted interventions aimed at reinforcing mucosal defenses and reducing vulnerability to HIV infection.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 5","pages":"e70240"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147760129","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of Inflammatory Markers, First-Trimester Biochemical Tests, and Gelsolin Levels in Patients With Second-Trimester Pregnancy Loss.","authors":"Betül Tokgöz Çakır, Gizem Aktemur, Gülşan Karabay, Nazan Vanlı Tonyalı, Zeynep Şeyhanlı, Dilara Duygulu Bulan, Kubilay Çanga, Hande Esra Koca Yıldırım, Ali Turhan Çağlar","doi":"10.1111/aji.70253","DOIUrl":"10.1111/aji.70253","url":null,"abstract":"<p><strong>Objective: </strong>The pathophysiological mechanisms underlying second trimester pregnancy loss are not yet fully elucidated. This study aimed to evaluate whether maternal serum gelsolin levels, together with hematological inflammatory indices and pregnancy related hormones, are associated with second trimester pregnancy loss.</p><p><strong>Methods: </strong>A total of 912 pregnant women were prospectively enrolled, and a nested matched case-control analysis was subsequently conducted including 112 participants (40 cases and 72 matched controls). The study was conducted at Ankara Etlik City Hospital between January and December 2024. The pregnancy loss group comprised 40 women who experienced second-trimester pregnancy loss, whereas the control group included 72 age- and body mass index-matched women with ongoing pregnancies. Maternal inflammatory markers-including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), systemic inflammatory response index (SIRI), systemic immune-inflammation index (SII), and aggregate index of systemic inflammation (AISI)-were evaluated. In addition, serum levels of human chorionic gonadotropin (hCG), pregnancy-associated plasma protein-A (PAPP-A), and gelsolin were measured and compared between groups.</p><p><strong>Results: </strong>Most hematological inflammatory indices, including NLR, PLR, MLR, SII, SIRI, and AISI, did not differ significantly between the groups. However, maternal serum PAPP-A levels were significantly lower in the pregnancy loss group (p = 0.012), whereas gelsolin levels were significantly higher (p = 0.034). Receiver operating characteristic (ROC) analysis demonstrated limited discriminatory performance for both markers. PAPP-A MoM showed an AUC of 0.644 (95% CI: 0.533-0.755, p = 0.012), with a cut-off value of <0.46 yielding a sensitivity of 77.5% and specificity of 91.7%. Despite its high specificity at the selected cut-off, overall discriminatory performance was limited. Gelsolin exhibited modest diagnostic performance with an AUC of 0.621 (95% CI: 0.501-0.741, p = 0.034), with a sensitivity of 57.5% and specificity of 44% at a threshold of >0.893 ng/mL.</p><p><strong>Conclusion: </strong>Maternal serum gelsolin levels were elevated and PAPP-A levels were reduced in pregnancies affected by second-trimester pregnancy loss. While gelsolin remained independently associated with pregnancy loss after adjustment, neither marker demonstrated sufficient discriminatory performance to be used as a standalone predictive tool. These findings may reflect underlying placental dysfunction and inflammatory dysregulation rather than overt systemic inflammation, and should be considered hypothesis-generating pending validation in larger prospective studies.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 5","pages":"e70253"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to Effect of Aurora kinase B on polyploidy and decidualization in mouse uterus.","authors":"","doi":"10.1111/aji.70257","DOIUrl":"https://doi.org/10.1111/aji.70257","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 5","pages":"e70257"},"PeriodicalIF":2.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147947542","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond the Barrier: Epithelial Cells as Immune Sentinels in the Female Genital Tract.","authors":"Lauren Jirik, Shreya Joshi, Aisha Nazli, Charu Kaushic","doi":"10.1111/aji.70243","DOIUrl":"10.1111/aji.70243","url":null,"abstract":"<p><p>Epithelial cells (ECs) of the female genital tract (FGT) serve as an essential barrier and the first line of defense against sexually transmitted pathogens. Beyond providing a physical barrier, these cells actively contribute to immune responses through pathogen recognition, cytokine release, and modulation of adaptive immune responses. Sexually transmitted viruses such as HIV-1 and HSV-2 must overcome the physical and functional barriers of the mucosal surface to establish infection. This review explores the intricate relationship between genital ECs and HIV-1 and HSV-2, emphasizing on how these interactions influence infection outcomes. We examine the innate immune responses of ECs in the upper and lower FGT, highlighting both their similarities and differences. Additionally, we delve into the mechanisms of pathogen recognition and virus-specific innate immune responses of genital ECs to HIV-1 and HSV-2. Deepening our understanding of epithelial-viral interactions is critical for identifying key determinants of susceptibility and resistance to sexually transmitted infections (STIs). Elucidating these mechanisms is essential for developing targeted strategies to enhance mucosal immunity, through novel antiviral therapies, vaccine strategies, or interventions to fortify epithelial defenses. Such advancements have the potential to improve protection against these infections and reduce their global burden.</p>","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 5","pages":"e70243"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13148466/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147832478","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148097195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148125558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":7665,"journal":{"name":"American Journal of Reproductive Immunology","volume":"95 5","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148097194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}