87 results on '"genital inflammation"'
Search Results
2. Seminal plasma S100A8/A9 as a potential biomarker of genital tract inflammation
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Qiu-Zi Shen, Yong-Feng Wang, Yi-Wei Fang, Yuan-Yao Chen, Li-Ting He, Yuan Zhang, Guo-Tao Liu, Kai Zhao, Chun-Yan Liu, Zun-Pan Fan, and Hui-Ping Zhang
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experimental autoimmune orchitis ,genital inflammation ,male infertility ,proteomics ,s100a8/a9 ,Diseases of the genitourinary system. Urology ,RC870-923 - Abstract
Infections and inflammatory reactions in the male genital tract are the leading causes of male infertility with a prevalence of 6%–10%, primarily affecting testicular and epididymal function and ultimately compromising sperm quality. However, most infertile patients with genital infection/inflammation are asymptomatic and easily overlooked. Traditional indicators, including white blood cells, elastase, and other components in semen, can reflect inflammation of the genital tract, but there is still a lack of a uniform standard method of detection. Therefore, it is necessary to explore reliable markers in semen that reflect the inflammatory status of the genital tract. Using the experimental autoimmune orchitis (EAO) model to simulate noninfectious chronic orchitis, we successfully collected ejaculated seminal fluid from EAO rats using optimized electrical stimulation devices. Proteomic analysis was performed using isobaric tags for relative and absolute quantification (iTRAQ). Compared to the control group, 55 upregulated and 105 downregulated proteins were identified in seminal plasma samples from the EAO group. In a preliminary screening, the inflammation-related protein S100A8/A9 was upregulated. We further verified that S100A8/A9 was increased in seminal plasma and highly expressed in testicular macrophages of the EAO model. In patients with oligoasthenospermia and genital tract infections, we also found that S100A8/A9 levels were remarkably increased in seminal plasma and testicular macrophages. S100A8/A9 in semen may be a potential biomarker for chronic genital inflammation. Our study provides a new potential biomarker for early diagnosis and further understanding of male infertility caused by genital inflammation.
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- 2024
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3. An analysis of the vaginal microbiota and cervicovaginal metabolomics in cervical lesions and cervical carcinoma
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Jie Ou, Yanan Kang, Medlegeh, Kun Fu, Yu Zhang, and Wenqing Yang
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Cervical intraepithelial neoplasia ,Cervical carcinoma ,Metabolome ,Microbiota ,Genital inflammation ,Science (General) ,Q1-390 ,Social sciences (General) ,H1-99 - Abstract
Background: To explore the role of vaginal microbiota and metabolomics in the progression of cervical dysplasia. Methods: The patient group consists of female patients with low-grade, high-grade cervical dysplasia, and cervical cancer. Normal cervix samples from health volunteers were used as controls. The metabolic fingerprints of cervicovaginal lavage were analyzed using liquid chromatography-mass spectrometry, while the vaginal microbiota was examined through 16S rRNA sequencing. Bioinformatic analysis was adopted to investigate the interplay between hosts and microbes. The vaginal metabolic and microbiota profiles of 90 female patients with cervical dysplasia and 10 controls were analyzed to discover the biological characteristics underlying the progression of cervical cancer. Results: We found that Valyl-Glutamate, N, N′-Diacetylbenzidine, and Oxidized glutathione, which were involved in oxidative stress response, were discriminators to distinguish the normal cervix, invasive cervical carcinomas, and CIN3 from others. Cervical carcinoma was characterized by a large variety of vaginal microbes (dominated by non-Lactobacillus communities) compared to the control. These microbes affected amino acid and nucleotide metabolism, producing metabolites with cervical carcinoma and genital inflammation compared to the control group. Conclusions: This study revealed that cervicovaginal metabolic profiles were determined by cervical cancer, vaginal microbiota, and their interplays. ROS metabolism can be used to discriminate normal cervix, CIN3, and invasive cervical carcinoma.
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- 2024
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4. Patterns of pediatric and adolescent female genital inflammation in China: an eight-year retrospective study of 49,175 patients in China
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Huihui Gao, Yuchen Zhang, Yanzheng Pan, Mengjia Zhao, Ye Qi, Mingming Zhou, Symphorosa S. C. Chan, Siyi Huang, Peige Song, Kun Tang, Liying Sun, and Changzheng Yuan
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pediatric and adolescent gynecology ,girls ,genital inflammation ,disease pattern ,vulnerable population ,pathogens ,Public aspects of medicine ,RA1-1270 - Abstract
BackgroundGenital inflammation is one of the most frequent clinical complaints among girls, which was easily overlooked by the general public. This study aimed to investigate the patterns and epidemiological characteristics of pediatric and adolescent female genital inflammation in China.MethodsA retrospective observational study (2011 to 2018) was conducted among all female patients under the age of 0–18 years at the Department of Pediatric and Adolescent Gynecology of The Children’s Hospital, Zhejiang University School of Medicine. Data were collected from the electronic medical records. The abnormal vaginal discharge of patient was collected for microbiological investigation by bacterial and fungal culture. Descriptive analysis was conducted to evaluate the genital inflammation pattern and epidemiological characteristics, including age, season, and type of infected pathogens.ResultsA total of 49,175 patients met the eligibility criteria of genital inflammation and 16,320 patients later came to the hospital for follow-up over the study period. The number of first-visit increased gradually from 3,769 in 2011 to 10,155 in 2018. The peak age of the first visit was 0–6 years old. Non-specific vulvovaginitis, lichen sclerosis, and labial adhesion were the top three genital inflammation. Among the top five potential common pathogens of vaginal infection, the prevalence of Haemophilus influenzae cases was the highest (31.42%, 203/646), followed by Streptococcus pyogenes (27.74%, 176/646), Candida albicans (14.09%, 91/646), Escherichia coli (8.51%, 55/646), and Staphylococcus aureus (6.35%, 41/636). The specific disease categories and pathogens of genital inflammation vary by age groups and season.ConclusionOur study summarizes the pattern of pediatric and adolescent female genital inflammation over an 8-year period in China, emphasizing the need for more public awareness, healthcare services and research in this field.
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- 2023
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5. The vaginal microbiota of women living with HIV on suppressive antiretroviral therapy and its relation to high-risk human papillomavirus infection
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Monserrat Chávez-Torres, Maria Gómez-Palacio-Schjetnan, Gustavo Reyes-Terán, Olivia Briceño, Santiago Ávila-Ríos, Karla Alejandra Romero-Mora, and Sandra Pinto-Cardoso
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Human immunodeficiency virus ,Antiretroviral therapy ,Human papillomavirus ,High-risk HPV ,Cervical cytology ,Genital inflammation ,Microbiology ,QR1-502 - Abstract
Abstract Background Few studies have investigated the vaginal microbiota (VM) in women living with HIV (WLWH) in the context of high-risk human papillomavirus (HR-HPV) infection, even though WLWH are at an increased risk of HPV-related malignancies, including cervical cancer. To explore the impact of HIV and HPV infection on the VM in WLWH, we determined the prevalence of HR-HPV infection and cervical cytologic abnormalities in a cohort of 44 WLWH and 39 seronegative-women (SNW), characterized the vaginal microbiota by 16S sequencing, assessed genital inflammation and systemic immune activation by multiplex bead assay and flow cytometry, respectively. Finally, we explored relationships between bacterial richness and diversity, the top 20 bacterial genera, genital inflammation and systemic immune activation. Results We found that HR-HPV prevalence was similar between WLWH and SNW. High-grade squamous intraepithelial lesions (HSIL) were only detected in WLWH negative for HR-HPV infection. In regression analyses, no risk factors were identified. Women co-infected with HIV and HR-HPV had the highest level of systemic immune activation, and these levels were significantly different compared with SNW without HR-HPV infection. Lactobacillus iners was the dominant Lactobacillus species in WLWH and SNW alike. Conclusion We found no evidence of differences in vaginal microbial richness and diversity, microbial community structure, and genital inflammation by HIV, HPV, or HIV and HPV status.
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- 2023
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6. Cervicovaginal Human Papillomavirus Genomes, Microbiota Composition and Cytokine Concentrations in South African Adolescents.
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Happel, Anna-Ursula, Balle, Christina, Havyarimana, Enock, Brown, Bryan, Maust, Brandon S., Feng, Colin, Yi, Byung H., Gill, Katherine, Bekker, Linda-Gail, Passmore, Jo-Ann S., Jaspan, Heather B., and Varsani, Arvind
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PAPILLOMAVIRUSES , *HUMAN papillomavirus , *SOUTH Africans , *DNA viruses , *SHOTGUN sequencing , *BACTERIAL vaginitis , *EUKARYOTIC genomes - Abstract
The interaction between cervicovaginal virome, bacteriome and genital inflammation has not been extensively investigated. We assessed the vaginal DNA virome from 33 South African adolescents (15–19 years old) using shotgun DNA sequencing of purified virions. We present analyses of eukaryote-infecting DNA viruses, with a focus on human papillomavirus (HPV) genomes and relate these to the vaginal bacterial microbiota (assessed by 16S rRNA gene sequencing) and cytokines (assessed by Luminex). The DNA virome included single-stranded (Anelloviridae, Genomoviridae) and double-stranded DNA viruses (Adenoviridae, Alloherpesviridae, Herpesviridae, Marseilleviridae, Mimiviridae, Polyomaviridae, Poxviridae). We identified 110 unique, complete HPV genomes within two genera (Alphapapillomavirus and Gammapapillomavirus) representing 40 HPV types and 12 species. Of the 40 HPV types identified, 35 showed positive co-infection patterns with at least one other type, mainly HPV-16. HPV-35, a high-risk genotype currently not targeted by available vaccines, was the most prevalent HPV type identified in this cohort. Bacterial taxa commonly associated with bacterial vaginosis also correlated with the presence of HPV. Bacterial vaginosis, rather than HPV, was associated with increased genital inflammation. This study lays the foundation for future work characterizing the vaginal virome and its role in women's health. [ABSTRACT FROM AUTHOR]
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- 2023
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7. The vaginal microbiota of women living with HIV on suppressive antiretroviral therapy and its relation to high-risk human papillomavirus infection.
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Chávez-Torres, Monserrat, Gómez-Palacio-Schjetnan, Maria, Reyes-Terán, Gustavo, Briceño, Olivia, Ávila-Ríos, Santiago, Romero-Mora, Karla Alejandra, and Pinto-Cardoso, Sandra
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PAPILLOMAVIRUSES , *HUMAN papillomavirus , *HIV-positive women , *PAPILLOMAVIRUS diseases , *ANTIRETROVIRAL agents , *HUMAN microbiota - Abstract
Background: Few studies have investigated the vaginal microbiota (VM) in women living with HIV (WLWH) in the context of high-risk human papillomavirus (HR-HPV) infection, even though WLWH are at an increased risk of HPV-related malignancies, including cervical cancer. To explore the impact of HIV and HPV infection on the VM in WLWH, we determined the prevalence of HR-HPV infection and cervical cytologic abnormalities in a cohort of 44 WLWH and 39 seronegative-women (SNW), characterized the vaginal microbiota by 16S sequencing, assessed genital inflammation and systemic immune activation by multiplex bead assay and flow cytometry, respectively. Finally, we explored relationships between bacterial richness and diversity, the top 20 bacterial genera, genital inflammation and systemic immune activation. Results: We found that HR-HPV prevalence was similar between WLWH and SNW. High-grade squamous intraepithelial lesions (HSIL) were only detected in WLWH negative for HR-HPV infection. In regression analyses, no risk factors were identified. Women co-infected with HIV and HR-HPV had the highest level of systemic immune activation, and these levels were significantly different compared with SNW without HR-HPV infection. Lactobacillus iners was the dominant Lactobacillus species in WLWH and SNW alike. Conclusion: We found no evidence of differences in vaginal microbial richness and diversity, microbial community structure, and genital inflammation by HIV, HPV, or HIV and HPV status. [ABSTRACT FROM AUTHOR]
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- 2023
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8. The efficacy and mechanism of acupuncture in the treatment of male infertility: A literature review.
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Jiaxing Feng, Hui He, Yu Wang, Xu Zhang, Xiuying Zhang, Tiantian Zhang, Mengyi Zhu, Xiaoke Wu, and Yuehui Zhang
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Fertility, a social, cultural, and medical issue, has aroused public attention because of its potential to predict future health. In recent years, the incidence of male infertility has increased significantly, and various risk factors, such as congenital factors, acquired factors, and idiopathic factors, have led to this situation. Male infertility causes substantial psychological and social distress in patients. With the implementation of the two-child policy, male infertility has brought enormous psychological and social pressure and huge economic burden to patients and the healthcare system. This has attracted the attention of not only men of childbearing age but also many male experts. The conventional therapeutic approaches for treating male infertility, including drugs, varicocele surgery, intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection, can restore fertility to a certain extent, but their efficacy is far from satisfactory, not to mention some adverse events. Therefore, acupuncture has been chosen by many men to treat their infertility and produced significant effects. In the present paper, the efficacy and mechanism of acupuncture in the treatment of male infertility were analyzed from different perspectives such as regulating hormone secretion, reducing inflammation, and improving semen parameters. The existing literature shows that acupuncture can effectively treat male infertility. [ABSTRACT FROM AUTHOR]
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- 2022
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9. Genital Immune Cell Activation and Tenofovir Gel Efficacy: A Case-Control Study.
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Liebenberg, Lenine J P, Passmore, Jo Ann S, Osman, Farzana, Jewanraj, Janine, Mtshali, Andile, Garcia-Lerma, J Gerardo, Heneine, Walid, Holder, Angela, Archary, Derseree, Ngcapu, Sinaye, Sivro, Aida, Mansoor, Leila E, Karim, Quarraisha Abdool, Karim, Salim S Abdool, and McKinnon, Lyle R
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DRUG efficacy , *CYTOKINES , *FLOW cytometry , *TENOFOVIR , *INFLAMMATION , *GENITAL diseases , *PHARMACEUTICAL gels - Abstract
Genital inflammation (GI) undermines topical human immunodeficiency virus (HIV) pre-exposure prophylaxis (PrEP) efficacy through unknown mechanisms. Here, associations between activated endocervical CD4 + T-cell numbers and higher deoxyadenosine triphosphate (dATP) concentrations suggest that competition for intracellular metabolites within HIV target cells may reduce the efficacy of antiretroviral-based PrEP in women with GI. [ABSTRACT FROM AUTHOR]
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- 2022
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10. Altered Vaginal Microbiota Composition Correlates With Human Papillomavirus and Mucosal Immune Responses in Women With Symptomatic Cervical Ectopy.
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López-Filloy, Mariana, Cortez, Flor J., Gheit, Tarik, Cruz y Cruz, Omar, Cruz-Talonia, Fernando, Chávez-Torres, Monserrat, Arteaga-Gómez, Cristina, Mancilla-Herrera, Ismael, Montesinos, Juan J., Cortés-Morales, Víctor Adrián, Aguilar, Cecilia, Tommasino, Massimo, Pinto-Cardoso, Sandra, and Rocha-Zavaleta, Leticia
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PAPILLOMAVIRUSES ,OROPHARYNX ,IMMUNE response ,SEXUALLY transmitted diseases ,HUMAN microbiota ,CHILDBEARING age ,VIRUS diseases - Abstract
Cervical ectopy is a benign condition of the lower genital tract that is frequently detected in women of reproductive age. Although cervical ectopy is regarded as a physiological condition, some women experience symptoms such as leucorrhoea, persistent bleeding and recurrent vaginal infections that require medical intervention. Cervical ectopy has not been linked to cervical cancer, but it is thought to facilitate the acquisition of sexually transmitted diseases (STDs), like Human Papillomavirus (HPV) infection, as it provides a favorable microenvironment for virus infection and dissemination. We and others have described the presence of oncogenic HPV types in women with symptomatic cervical ectopy. The relevance of this finding and the impact of symptomatic cervical ectopy on the cervicovaginal microenvironment (vaginal microbiota, immune and inflammatory responses) are currently unknown. To shed some light into the interplay between HPV, the vaginal microbiota and mucosal immune and inflammatory responses in the context of this condition, we enrolled 156 women with symptomatic cervical ectopy and determined the presence of HPV using a type-specific multiplex genotyping assay. Overall, HPV was detected in 54.48% women, oncogenic HPV types were found in more than 90% of HPV-positive cases. The most prevalent HPV types were HPV16 (29.4%), HPV31 (21.17%) and HPV18 (15.29%). Next, we evaluated the vaginal microbial composition and diversity by 16S rDNA sequencing, and quantified levels of cytokines and chemokines by flow cytometry using bead-based multiplex assays in a sub-cohort of 63 women. IL-21 and CXCL9 were significantly upregulated in HPV-positive women (p =0.0002 and p =0.013, respectively). Women with symptomatic cervical ectopy and HPV infection had increased diversity (p <0.001), and their vaginal microbiota was enriched in bacterial vaginosis-associated anaerobes (Sneathia , Shuttleworthia , Prevotella , and Atopobium) and depleted in Lactobacillus spp. Furthermore, the vaginal microbiota of women with symptomatic cervical ectopy and HPV infection correlated with vaginal inflammation (IL-1β, rho=0.56, p =0.0004) and increased mucosal homeostatic response (IL-22, rho=0.60, p =0.0001). Taken together, our results suggest that HPV infection and dysbiotic vaginal communities could favor a vaginal microenvironment that might delay the recovery of the cervical epithelium in women with symptomatic cervical ectopy and favor STDs acquisition. [ABSTRACT FROM AUTHOR]
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- 2022
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11. Altered Vaginal Microbiota Composition Correlates With Human Papillomavirus and Mucosal Immune Responses in Women With Symptomatic Cervical Ectopy
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Mariana López-Filloy, Flor J. Cortez, Tarik Gheit, Omar Cruz y Cruz, Fernando Cruz-Talonia, Monserrat Chávez-Torres, Cristina Arteaga-Gómez, Ismael Mancilla-Herrera, Juan J. Montesinos, Víctor Adrián Cortés-Morales, Cecilia Aguilar, Massimo Tommasino, Sandra Pinto-Cardoso, and Leticia Rocha-Zavaleta
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human papillomavirus ,vaginal microbiota ,mucosal immune responses ,genital inflammation ,cervicovaginal mucus ,cervical ectopy ,Microbiology ,QR1-502 - Abstract
Cervical ectopy is a benign condition of the lower genital tract that is frequently detected in women of reproductive age. Although cervical ectopy is regarded as a physiological condition, some women experience symptoms such as leucorrhoea, persistent bleeding and recurrent vaginal infections that require medical intervention. Cervical ectopy has not been linked to cervical cancer, but it is thought to facilitate the acquisition of sexually transmitted diseases (STDs), like Human Papillomavirus (HPV) infection, as it provides a favorable microenvironment for virus infection and dissemination. We and others have described the presence of oncogenic HPV types in women with symptomatic cervical ectopy. The relevance of this finding and the impact of symptomatic cervical ectopy on the cervicovaginal microenvironment (vaginal microbiota, immune and inflammatory responses) are currently unknown. To shed some light into the interplay between HPV, the vaginal microbiota and mucosal immune and inflammatory responses in the context of this condition, we enrolled 156 women with symptomatic cervical ectopy and determined the presence of HPV using a type-specific multiplex genotyping assay. Overall, HPV was detected in 54.48% women, oncogenic HPV types were found in more than 90% of HPV-positive cases. The most prevalent HPV types were HPV16 (29.4%), HPV31 (21.17%) and HPV18 (15.29%). Next, we evaluated the vaginal microbial composition and diversity by 16S rDNA sequencing, and quantified levels of cytokines and chemokines by flow cytometry using bead-based multiplex assays in a sub-cohort of 63 women. IL-21 and CXCL9 were significantly upregulated in HPV-positive women (p=0.0002 and p=0.013, respectively). Women with symptomatic cervical ectopy and HPV infection had increased diversity (p
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- 2022
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12. Performance of Softcup® menstrual cup and vulvovaginal swab samples for detection and quantification of genital cytokines.
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Pillay, Nashlin, Mzobe, Gugulethu Favourate, Letsoalo, Marothi, Kama, Asavela Olona, Mtshali, Andile, Magini, Stanley Nzuzo, Singh, Nikkishia, Govender, Vani, Samsunder, Natasha, Naidoo, Megeshinee, Moodley, Dhayendre, Baxter, Cheryl, Archary, Derseree, and Ngcapu, Sinaye
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FEMININE hygiene products , *CYTOKINES , *BIOLOGICAL specimens , *GENITALIA , *BIOMARKERS - Abstract
Cytokines are important mediators of immunity in the female genital tract, and their levels may be associated with various reproductive health outcomes. However, the measurement of cytokines and chemokines in vaginal fluid samples may be influenced by a variety of factors, each with the potential to affect the sensitivity and accuracy of the assay, including the interpretation and comparison of data. We measured and compared cytokine milieu in samples collected via Softcup® menstrual cup versus vulvovaginal swabs. One hundred and eighty vulvovaginal swabs from CAPRISA 088 and 42 Softcup supernatants from CAPRISA 016 cohorts of pregnant women were used to measure the concentrations of 28 cytokines through multiplexing. Cytokines measured in this study were detectable in each of the methods however, SoftCup supernatants showed consistently, higher detectability, expression ratios, and mean concentration of cytokines than vulvovaginal swabs. While mean concentrations differed, the majority of cytokines correlated between SoftCup supernatants and vulvovaginal swabs. Additionally, there were no significant differences in a number of participants between the two sampling methods for the classification of genital inflammation. Our findings suggest that SoftCup supernatants and vulvovaginal swab samples are suitable for the collection of genital specimens to study biological markers of genital inflammatory response. However, the Softcup menstrual cup performs better for the detection and quantification of soluble biomarkers that are found in low concentrations in cervicovaginal fluid. [ABSTRACT FROM AUTHOR]
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- 2024
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13. Etiopathogenesis of reproductive tract infections and the emerging role of bitter taste receptors: A scoping review
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Menizibeya O Welcome, Abraham Jeremiah, Dennis O Allagoa, Senol Dane, and Vladimir A Pereverzev
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infection ,genital inflammation ,reproduction ,reproductive tract infections ,bitter taste receptor ,etiopathogenesis ,cytokines ,Medicine - Abstract
Reproductive tract infections pose an immense public health concern worldwide as over 600 million new cases are recorded annually along with several complications, including infertility, ectopic pregnancy, preterm delivery, and neonatal death. Despite improved understanding of the mechanisms of pathogenic invasion, the etiopathogenesis of reproductive tract infections is yet to be completely understood. Recent data has suggested a critical role of bitter taste receptors of the reproductive tract in etiopathogenesis of reproductive tract infections. Here, we review the literature on current etiopathogenesis of reproductive tract infections and the role of bitter taste receptors of the reproductive tract in etiopathogenesis of reproductive tract infections. Emerging evidence suggests a critical role of microbiota disorder of the reproductive tract in reproductive tract infections. Several bacterial, protozoan parasitic, helminthic parasitic and viral pathogens have been identified as causative agents of reproductive tract infections. These pathogens subvert host defenses and activate specific architectural units of the uroepithelium such as Toll-like receptors, which recognize conserved motifs on the pathogens. The activated Toll-like receptors mediate downstream signaling, stimulating nuclear factor-κB, which in turn activates the production of proinflammatory cytokines. This pathway is also associated with recruitment of immunocytes to the site of aggression and release of proteinases, which drive tissue damage in the reproductive tract. Defects in detection of pathogenic components by the bitter taste receptors of the reproductive tract may play a critical role in the etiopathogenesis of reproductive tract infections. This review provides important information for identification of novel frontiers for the treatment of reproductive tract infections.
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- 2021
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14. Cervicovaginal DNA Virome Alterations Are Associated with Genital Inflammation and Microbiota Composition
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Emily A. Kaelin, Peter T. Skidmore, Paweł Łaniewski, LaRinda A. Holland, Dana M. Chase, Melissa M. Herbst-Kralovetz, and Efrem S. Lim
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cervicovaginal virome ,cervical cancer ,human papillomavirus ,HPV ,Lactobacillus species ,genital inflammation ,Microbiology ,QR1-502 - Abstract
ABSTRACT While the link between the cervicovaginal bacterial microbiome, human papillomavirus (HPV) infection, and cervical cancer is recognized (P. Łaniewski, D. Barnes, A. Goulder, H. Cui, et al., Sci. Rep. 8:7593, 2018, http://dx.doi.org/10.1038/s41598-018-25879-7; A. Mitra, D. A. MacIntyre, Y. S. Lee, A. Smith, et al., Sci. Rep. 5:16865, 2015, http://dx.doi.org/10.1038/srep16865; A. Mitra, D. A. MacIntyre, J. R. Marchesi, Y. S. Lee, et al., Microbiome 4:58, 2016, http://dx.doi.org/10.1186/s40168-016-0203-0; J. Norenhag, J. Du, M. Olovsson, H. Verstraelen, et al., BJOG, 127:171–180, 2020, http://dx.doi.org/10.1111/1471-0528.15854; E. O. Dareng, B. Ma, A. O. Famooto, S. N. Adebamowo, et al., Epidemiol. Infect. 144:123–137, 2016, http://dx.doi.org/10.1017/S0950268815000965; A. Audirac-Chalifour, K. Torres-Poveda, M. Bahena-Roman, J. Tellez-Sosa et al., PLoS One 11:e0153274, 2016, http://dx.doi.org/10.1371/journal.pone.0153274; M. Di Paola, C. Sani, A. M. Clemente, A. Iossa, et al., Sci. Rep. 7:10200, 2017, http://dx.doi.org/10.1038/s41598-017-09842-6), the role of the cervicovaginal virome remains poorly understood. In this pilot study, we conducted metagenomic next-generation sequencing of cervicovaginal lavage specimens to investigate the relationship between the cervicovaginal DNA virome, bacterial microbiome, genital inflammation, and HPV infection. Specific virome alterations were associated with features of the local microenvironment related to HPV persistence and progression to cervical cancer. Cervicovaginal viromes clustered distinctly by genital inflammation state. Genital inflammation was associated with decreased virome richness and alpha diversity and an increased abundance of Anelloviridae species from the genus Alphatorquevirus. Lactobacillus bacteriophages were closely associated with increased Lactobacillus abundance, consistent with phage-host relationships. Interestingly, bacteria-bacteriophage transkingdom interactions were linked to genital inflammation and showed specific interactions with bacterial vaginosis-associated bacteria, including Gardnerella, Prevotella, and Sneathia. Taken together, our results reveal prominent virome interactions with features of the cervicovaginal microenvironment that are associated with HPV and cervical cancer. These findings expand our understanding of the cervicovaginal host-microbiome interactions in women’s health. IMPORTANCE HPV infection is an established risk factor for cervical cancer. However, more broadly, the role of the cervicovaginal virome in cervical cancer progression is not well understood. Here, we identified cervicovaginal DNA virome alterations associated with local microenvironment factors (vaginal microbiota and genital inflammation) that influence HPV persistence and progression to cervical cancer. These findings indicate that the cervicovaginal virome plays an important role in women’s health.
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- 2022
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15. Persistent, Asymptomatic Colonization with Candida is Associated with Elevated Frequencies of Highly Activated Cervical Th17-Like Cells and Related Cytokines in the Reproductive Tract of South African Adolescents
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Anna-Ursula Happel, Melanie Gasper, Christina Balle, Iyaloo Konstantinus, Hoyam Gamieldien, Smritee Dabee, Katherine Gill, Linda-Gail Bekker, Jo-Ann S. Passmore, and Heather B. Jaspan
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vaginal candidiasis ,Sub-Saharan Africa ,genital inflammation ,HIV target cells ,mucosal immunity ,Microbiology ,QR1-502 - Abstract
ABSTRACT Cervicovaginal inflammation, nonoptimal microbiota, T-cell activation, and hormonal contraceptives may increase HIV risk, yet associations between these factors and subclinical Candida colonization or hyphae are unknown. We collected cervicovaginal samples from 94 South African adolescents, aged 15 to 19 years, who were randomized to injectable norethisterone enanthate (Net-En), an etonorgesterol/ethinyl estradiol vaginal ring (NuvaRing), or oral contraceptives in the UChoose trial (NCT02404038) at baseline and 16 weeks post-randomization. We assessed cervicovaginal samples for subclinical Candida colonization (by quantitative PCR [qPCR]), hyphae (by Gram stain), microbiota composition (by 16S rRNA gene sequencing), cytokine concentrations (by Luminex), and cervical T-cell phenotypes and activation (by multiparameter flow cytometry). While hormonal contraceptive type did not influence incidence of Candida colonization or hyphae, hyphae presence was associated with significantly elevated concentrations of IL-22, IL-17A and IL-17F, all produced by Th17 cells, but not of other cytokines, such as IL-1β or IL-6, after adjustment for confounders. Subclinical Candida colonization was associated with reduced frequencies of Th17-like cells and elevated frequencies of CCR6-CCR10 T cells. Women with Candida hyphae were less likely to have bacterial vaginosis (BV). Persistent, subclinical colonization with Candida over 16 weeks was associated with significant increases in Th17-related cytokine concentrations and highly activated Th17-like and CCR6-CCR10 T-cell frequencies. These data suggest that vaginal Candida colonization and hyphae increase Th17-related cytokines, but not overall female genital tract inflammation in Sub-Saharan African adolescents. Persistent Candida colonization, even when asymptomatic, may increase Th17 cell frequencies and related cytokines and thereby could subsequently increase HIV risk, although the causal relationship requires confirmation. IMPORTANCE Sub-Saharan African female adolescents are globally at the highest risk of HIV acquisition, and genital inflammation, microbial dysbiosis, and cervical HIV target cell activation are thought to contribute to this risk. Previously, the relationship between these mucosal factors and subclinical vaginal Candida colonization or hyphae has not been described, and the role of HIV-susceptible Th17 cells in mediating anti-Candida immunity in the human female genital tract has not been clearly established. We show that presence of yeast hyphae was associated with increases in Th17 cell-related cytokines and the absence of microbial dysbiosis, and that persistent Candida colonization resulted in significant increases in Th17-related cytokines and highly activated Th17-like cell frequencies. Our results suggest that Th17 cells are important for anti-Candida immunity in the human female genital tract and that prolonged vaginal Candida colonization may contribute to increased HIV risk in Sub-Saharan African adolescents by increasing HIV target cell frequencies and activation.
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- 2022
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16. Immunometabolic Analysis of Mobiluncus mulieris and Eggerthella sp. Reveals Novel Insights Into Their Pathogenic Contributions to the Hallmarks of Bacterial Vaginosis.
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McKenzie, Ross, Maarsingh, Jason D., Łaniewski, Paweł, and Herbst-Kralovetz, Melissa M.
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BIOGENIC amines ,BACTERIAL vaginitis ,PATHOGENIC microorganisms ,VAGINAL discharge ,ENERGY metabolism ,PREMATURE labor ,AMINO acid metabolism - Abstract
The cervicovaginal microbiome plays an important role in protecting women from dysbiosis and infection caused by pathogenic microorganisms. In healthy reproductive-age women the cervicovaginal microbiome is predominantly colonized by protective Lactobacillus spp. The loss of these protective bacteria leads to colonization of the cervicovaginal microenvironment by pathogenic microorganisms resulting in dysbiosis and bacterial vaginosis (BV). Mobiluncus mulieris and Eggerthella sp. are two of the many anaerobes that can contribute to BV, a condition associated with multiple adverse obstetric and gynecological outcomes. M. mulieris has been linked to high Nugent scores (relating to BV morphotypes) and preterm birth (PTB), whilst some bacterial members of the Eggerthellaceae family are highly prevalent in BV, and identified in ~85-95% of cases. The functional impact of M. mulieris and Eggerthella sp. in BV is still poorly understood. To determine the individual immunometabolic contributions of Eggerthella sp. and M. mulieris within the cervicovaginal microenvironment, we utilized our well-characterized human three-dimensional (3-D) cervical epithelial cell model in combination with multiplex immunoassays and global untargeted metabolomics approaches to identify key immune mediators and metabolites related to M. mulieris and Eggerthella sp. infections. We found that infection with M. mulieris significantly elevated multiple proinflammatory markers (IL-6, IL-8, TNF-α and MCP-1) and altered metabolites related to energy metabolism (nicotinamide and succinate) and oxidative stress (cysteinylglycine, cysteinylglycine disulfide and 2-hydroxygluatrate). Eggerthella sp. infection significantly elevated multiple sphingolipids and glycerolipids related to epithelial barrier function, and biogenic amines (putrescine and cadaverine) associated with elevated vaginal pH, vaginal amine odor and vaginal discharge. Our study elucidated that M. mulieris elevated multiple proinflammatory markers relating to PTB and STI acquisition, as well as altered energy metabolism and oxidative stress, whilst Eggerthella sp. upregulated multiple biogenic amines associated with the clinical diagnostic criteria of BV. Future studies are needed to evaluate how these bacteria interact with other BV-associated bacteria within the cervicovaginal microenvironment. [ABSTRACT FROM AUTHOR]
- Published
- 2021
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17. An analysis of the vaginal microbiota and cervicovaginal metabolomics in cervical lesions and cervical carcinoma.
- Author
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Ou J, Kang Y, Medlegeh, Fu K, Zhang Y, and Yang W
- Abstract
Background: To explore the role of vaginal microbiota and metabolomics in the progression of cervical dysplasia., Methods: The patient group consists of female patients with low-grade, high-grade cervical dysplasia, and cervical cancer. Normal cervix samples from health volunteers were used as controls. The metabolic fingerprints of cervicovaginal lavage were analyzed using liquid chromatography-mass spectrometry, while the vaginal microbiota was examined through 16S rRNA sequencing. Bioinformatic analysis was adopted to investigate the interplay between hosts and microbes. The vaginal metabolic and microbiota profiles of 90 female patients with cervical dysplasia and 10 controls were analyzed to discover the biological characteristics underlying the progression of cervical cancer., Results: We found that Valyl-Glutamate, N, N'-Diacetylbenzidine, and Oxidized glutathione, which were involved in oxidative stress response, were discriminators to distinguish the normal cervix, invasive cervical carcinomas, and CIN3 from others. Cervical carcinoma was characterized by a large variety of vaginal microbes (dominated by non-Lactobacillus communities) compared to the control. These microbes affected amino acid and nucleotide metabolism, producing metabolites with cervical carcinoma and genital inflammation compared to the control group., Conclusions: This study revealed that cervicovaginal metabolic profiles were determined by cervical cancer, vaginal microbiota, and their interplays. ROS metabolism can be used to discriminate normal cervix, CIN3, and invasive cervical carcinoma., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)
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- 2024
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18. Recent Semen Exposure Impacts the Cytokine Response and Bacterial Vaginosis in Women
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Khanyisile Mngomezulu, Gugulethu F. Mzobe, Andile Mtshali, Farzana Osman, Lenine J. P. Liebenberg, Nigel Garrett, Ravesh Singh, Anne Rompalo, Adrian Mindel, Salim S. Abdool Karim, Quarraisha Abdool Karim, Cheryl Baxter, and Sinaye Ngcapu
- Subjects
semen exposure ,prostate specific antigen ,genital inflammation ,cytokines ,bacterial vaginosis ,Immunologic diseases. Allergy ,RC581-607 - Abstract
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 Trichomonas vaginalis detection. Multivariable models, adjusted for age, sexually transmitted infections, BV, current contraception use and condom use, were used to assess the impact of semen exposure on biomarkers of inflammation and BV.ResultsPresence of PSA, indicating recent semen exposure within 48 hours prior to sampling, was observed in menstrual cup supernatants of 17% (43/248) of women. Of these women, 70% (30/43) had self-reported condom use at their last sex act and 84% (36/43) had BV (Nugent score >7). PSA presence was significantly associated with prevalent BV (Relative Risk (RR), 2.609; 95% Confidence Interval (CI), 1.104 - 6.165; p = 0.029). Furthermore, women with detectable PSA had high median concentrations of macrophage inflammatory protein- beta (MIP-1α, p=0.047) and low median concentration of the stem cell growth factor beta (SCGF-β, p=0.038) compared to those without PSA.ConclusionA degree of discordance between self-reports of consistent condom use and PSA positivity was observed. There was also evidence of a relationship between recent semen exposure, BV prevalence and altered cytokine concentrations. These findings suggest that PSA, as a semen biomarker, should be taken into consideration when investigating biological markers in the female genital tract and self-reported condom use in studies on reproductive and sexual health.
- Published
- 2021
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19. Recent Semen Exposure Impacts the Cytokine Response and Bacterial Vaginosis in Women.
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Mngomezulu, Khanyisile, Mzobe, Gugulethu F., Mtshali, Andile, Osman, Farzana, Liebenberg, Lenine J. P., Garrett, Nigel, Singh, Ravesh, Rompalo, Anne, Mindel, Adrian, Karim, Salim S. Abdool, Karim, Quarraisha Abdool, Baxter, Cheryl, and Ngcapu, Sinaye
- Subjects
BACTERIAL vaginitis ,SEMEN ,SEXUALLY transmitted diseases ,STEM cell factor ,PROSTATE-specific antigen ,UNSAFE sex - Abstract
Background: The 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. Methods: At 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 Trichomonas vaginalis detection. Multivariable models, adjusted for age, sexually transmitted infections, BV, current contraception use and condom use, were used to assess the impact of semen exposure on biomarkers of inflammation and BV. Results: Presence of PSA, indicating recent semen exposure within 48 hours prior to sampling, was observed in menstrual cup supernatants of 17% (43/248) of women. Of these women, 70% (30/43) had self-reported condom use at their last sex act and 84% (36/43) had BV (Nugent score >7). PSA presence was significantly associated with prevalent BV (Relative Risk (RR), 2.609; 95% Confidence Interval (CI), 1.104 - 6.165; p = 0.029). Furthermore, women with detectable PSA had high median concentrations of macrophage inflammatory protein- beta (MIP-1α, p=0.047) and low median concentration of the stem cell growth factor beta (SCGF-β, p=0.038) compared to those without PSA. Conclusion: A degree of discordance between self-reports of consistent condom use and PSA positivity was observed. There was also evidence of a relationship between recent semen exposure, BV prevalence and altered cytokine concentrations. These findings suggest that PSA, as a semen biomarker, should be taken into consideration when investigating biological markers in the female genital tract and self-reported condom use in studies on reproductive and sexual health. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
20. Members of Prevotella Genus Distinctively Modulate Innate Immune and Barrier Functions in a Human Three-Dimensional Endometrial Epithelial Cell Model.
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Ilhan, Zehra Esra, Łaniewski, Paweł, Tonachio, Adriana, and Herbst-Kralovetz, Melissa M
- Subjects
- *
EPITHELIAL cells , *PREVOTELLA , *MOUTH , *BACTERIAL vaginitis , *GENITALIA , *PROTEINS , *RESEARCH , *SCANNING electron microscopy , *RESEARCH methodology , *GRAM-negative anaerobic bacteria , *MEDICAL cooperation , *EVALUATION research , *COMPARATIVE studies , *IMMUNITY , *RESEARCH funding , *CELL lines , *ENDOMETRIUM - Abstract
Background: Prevotella species are commonly isolated from the reproductive tract of women with obstetric/gynecologic health complications. However, contributions of this genus to changes in local microenvironment are not well characterized. Our objective was to evaluate species-specific effects of Prevotella on the human endometrial epithelium.Methods: Thirteen Prevotella strains, originally isolated from the human oral cavity, amniotic fluid, endometrium, or vagina (including women with bacterial vaginosis), were obtained from BEI and ATCC resources. Bacteria were evaluated in silico and in vitro using human endometrial epithelial cells (EEC) grown as monolayers or a 3-dimensional (3D) model.Results: Genomic characterization illustrated metabolic and phylogenetic diversity of Prevotella genus. Among tested species, P. disiens exhibited cytotoxicity. Scanning electron microscopy analysis of the 3D EEC model revealed species-specific colonization patterns and alterations of ultracellular structures. Infection with sialidase-producing P. timonensis resulted in elongated microvilli, and increased MUC3 and MUC4 expression. Infections with Prevotella species, including P. bivia, did not result in significant proinflammatory activation of EEC.Conclusions: Collectively, findings indicate that Prevotella species are metabolically diverse and overall not cytotoxic or overtly inflammatory in EEC; however, these bacteria can form biofilms, alter barrier properties of the endometrial epithelium, and ultimately impact colonization of secondary colonizers. [ABSTRACT FROM AUTHOR]- Published
- 2020
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21. Determinants of Vaginal Microbiota Composition
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Yumna Moosa, Douglas Kwon, Tulio de Oliveira, and Emily B. Wong
- Subjects
vaginal microbiota ,vaginal dysbiosis ,genital inflammation ,microbiota transmission ,HIV acquisition ,Microbiology ,QR1-502 - Abstract
There is increasing evidence that the composition of a woman's vaginal microbiota significantly influences her sexual and reproductive health, including her risk of miscarriage, preterm birth, HIV and other sexually transmitted infections. Efforts to modulate the vaginal microbiota using antibiotic or probiotic therapy have shown limited lasting or reliable success. To explore the natural dynamics and causal pathways responsible for heterogeneity of vaginal microbiota composition we review the existing literature on its determinants, from the perspective of microorganism- and host-related factors. We then discuss how molecular approaches can be harnessed to advance our understanding of individual and population-level vaginal microbiota composition patterns. Work has been done to investigate determinants of microbial composition patterns in other body niches, but very little in the female genital tract so far. There is an urgent need to better understand vaginal microbiota composition patterns, across the lifespan, outside of the context of sexual health clinics, and in Sub-Saharan African women in whom vaginal microbiota composition may be a risk factor for HIV acquisition. More work is needed to clarify causal relationships between clinical symptoms, host genetic, host behavior, and molecular vaginal microbiota profiles. These insights will lay the groundwork for novel and targeted interventional approaches to improve women's sexual and reproductive health.
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- 2020
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22. Determinants of Vaginal Microbiota Composition.
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Moosa, Yumna, Kwon, Douglas, de Oliveira, Tulio, and Wong, Emily B.
- Subjects
SEXUALLY transmitted diseases ,GENITALIA ,SEXUAL health ,REPRODUCTIVE health ,ORGASM ,PREMATURE labor - Abstract
There is increasing evidence that the composition of a woman's vaginal microbiota significantly influences her sexual and reproductive health, including her risk of miscarriage, preterm birth, HIV and other sexually transmitted infections. Efforts to modulate the vaginal microbiota using antibiotic or probiotic therapy have shown limited lasting or reliable success. To explore the natural dynamics and causal pathways responsible for heterogeneity of vaginal microbiota composition we review the existing literature on its determinants, from the perspective of microorganism- and host-related factors. We then discuss how molecular approaches can be harnessed to advance our understanding of individual and population-level vaginal microbiota composition patterns. Work has been done to investigate determinants of microbial composition patterns in other body niches, but very little in the female genital tract so far. There is an urgent need to better understand vaginal microbiota composition patterns, across the lifespan, outside of the context of sexual health clinics, and in Sub-Saharan African women in whom vaginal microbiota composition may be a risk factor for HIV acquisition. More work is needed to clarify causal relationships between clinical symptoms, host genetic, host behavior, and molecular vaginal microbiota profiles. These insights will lay the groundwork for novel and targeted interventional approaches to improve women's sexual and reproductive health. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
23. Personal and Clinical Vaginal Lubricants: Impact on Local Vaginal Microenvironment and Implications for Epithelial Cell Host Response and Barrier Function.
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Wilkinson, Ellen M, Łaniewski, Paweł, Herbst-Kralovetz, Melissa M, and Brotman, Rebecca M
- Subjects
- *
EPITHELIAL cells , *LUBRICATION & lubricants , *INFLAMMATORY mediators , *SEXUAL intercourse , *CELL survival - Abstract
Background: A majority of US women report past use of vaginal lubricants to enhance the ease and comfort of intimate sexual activities. Lubricants are also administered frequently in clinical practice. We sought to investigate if hyperosmolar lubricants are toxic to the vaginal mucosal epithelia.Methods: We tested a panel of commercially available lubricants across a range of osmolalities in human monolayer vaginal epithelial cell (VEC) culture and a robust 3-dimensional (3-D) VEC model. The impact of each lubricant on cellular morphology, cytotoxicity, barrier targets, and the induction of inflammatory mediators was examined. Conceptrol, containing nonoxynol-9, was used as a cytotoxicity control.Results: We observed a loss of intercellular connections, and condensation of chromatin, with increasing lubricant osmolality. EZ Jelly, K-Y Jelly, Astroglide, and Conceptrol induced cytotoxicity in both models at 24 hours. There was a strong positive correlation (r = 0.7326) between lubricant osmolality and cytotoxicity in monolayer VECs, and cell viability was reduced in VECs exposed to all the lubricants tested for 24 hours, except McKesson. Notably, select lubricants altered cell viability, barrier targets, and inflammatory mediators in 3-D VECs.Conclusions: These findings indicate that hyperosmolar lubricants alter VEC morphology and are selectively cytotoxic, inflammatory, and barrier disrupting in the 3-D VEC model. [ABSTRACT FROM AUTHOR]- Published
- 2019
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24. What Does the Future Hold for CAPRISA?
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Abdool Karim, Salim S., Baxter, Cheryl, Abdool Karim, Quarraisha, Abdool Karim, Quarraisha, editor, Abdool Karim, Salim S., editor, and Baxter, Cheryl, editor
- Published
- 2017
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25. Semen IgM, IgG1, and IgG3 Differentially Associate With Pro-Inflammatory Cytokines in HIV-Infected Men
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Thevani Pillay, Parveen Sobia, Abraham Jacobus Olivier, Kapil Narain, Lenine J. P. Liebenberg, Sinaye Ngcapu, Mesuli Mhlongo, Jo-Ann S. Passmore, Cheryl Baxter, and Derseree Archary
- Subjects
semen ,HIV ,HIV-specific antibodies ,immunoglobulins ,cytokines ,genital inflammation ,Immunologic diseases. Allergy ,RC581-607 - Abstract
Genital inflammation significantly increases the risk for HIV infection. The seminal environment is enriched in pro-inflammatory cytokines and chemokines. Here, we investigated the interplay between semen cytokines and humoral immunity to understand whether the characteristics of semen antibodies are associated with genital inflammation. In 36 HIV-infected and 40 HIV-uninfected mens' semen, HIV-specific antibodies (gp120, gp41, p66, and p24), immunoglobulin (Ig) subclasses, isotypes and cytokines, using multiplex assays, were measured. Semen IgG1, IgG3, and IgM were significantly higher in HIV-infected compared to HIV-uninfected men (p < 0.05). In HIV-uninfected men, pro-inflammatory cytokines IL-6, IL-8, and MCP-1 significantly correlated with IgG1 and total IgG (IgG1+IgG2+IgG3+IgG4) (both r≥0.55; p≤0.001). Total IgG in HIV-infected men correlated to HIV-specific antibodies in the semen irrespective of antiretroviral (ARV) use. In HIV-infected, ARV-treated men, p66 and gp41-specific antibodies were inversely correlated with IL-6 and MIP-1α (both r≥−0.65, p≤0.03). In HIV-infected, ARV-naïve men, p24 and gp120-specific antibodies correlated significantly with pro-inflammatory TNF-α (r≥0.44, p≤0.03), while p24 antibodies correlated significantly with chemokine MIP-1β (r = 0.45; p = 0.02). Local cytokines/chemokines were associated with the mucosal-specific Ig subclasses which likely effect specific antibody functions. Together, these data inform on mucosal-specific immunity that may be elicited in the male genital tract (MGT) in future vaccines and/or combination HIV prevention strategies.
- Published
- 2019
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26. Inflammatory Cytokine Profiles of Semen Influence Cytokine Responses of Cervicovaginal Epithelial Cells
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Cosnet L. Rametse, Anthonio O. Adefuye, Abraham J. Olivier, Lyle Curry, Hoyam Gamieldien, Wendy A. Burgers, David A. Lewis, Anna-Lise Williamson, Arieh A. Katz, and Jo-Ann S. Passmore
- Subjects
genital inflammation ,HIV ,semen ,cytokines ,HeLa ,interleukins ,Immunologic diseases. Allergy ,RC581-607 - Abstract
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.
- Published
- 2018
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27. Cervicovaginal Human Papillomavirus Genomes, Microbiota Composition and Cytokine Concentrations in South African Adolescents
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Anna-Ursula Happel, Christina Balle, Enock Havyarimana, Bryan Brown, Brandon S. Maust, Colin Feng, Byung H. Yi, Katherine Gill, Linda-Gail Bekker, Jo-Ann S. Passmore, Heather B. Jaspan, and Arvind Varsani
- Subjects
Infectious Diseases ,Virology ,HPV ,Alphapapillomavirus ,Gammapapillomavirus ,whole genome ,DNA viruses ,vaginal virome ,genital inflammation ,microbiome ,Sub-Saharan Africa ,women’s health - Abstract
The interaction between cervicovaginal virome, bacteriome and genital inflammation has not been extensively investigated. We assessed the vaginal DNA virome from 33 South African adolescents (15–19 years old) using shotgun DNA sequencing of purified virions. We present analyses of eukaryote-infecting DNA viruses, with a focus on human papillomavirus (HPV) genomes and relate these to the vaginal bacterial microbiota (assessed by 16S rRNA gene sequencing) and cytokines (assessed by Luminex). The DNA virome included single-stranded (Anelloviridae, Genomoviridae) and double-stranded DNA viruses (Adenoviridae, Alloherpesviridae, Herpesviridae, Marseilleviridae, Mimiviridae, Polyomaviridae, Poxviridae). We identified 110 unique, complete HPV genomes within two genera (Alphapapillomavirus and Gammapapillomavirus) representing 40 HPV types and 12 species. Of the 40 HPV types identified, 35 showed positive co-infection patterns with at least one other type, mainly HPV-16. HPV-35, a high-risk genotype currently not targeted by available vaccines, was the most prevalent HPV type identified in this cohort. Bacterial taxa commonly associated with bacterial vaginosis also correlated with the presence of HPV. Bacterial vaginosis, rather than HPV, was associated with increased genital inflammation. This study lays the foundation for future work characterizing the vaginal virome and its role in women’s health.
- Published
- 2023
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28. Characterization of the Genital Mucosa Immune Profile to Distinguish Phases of the Menstrual Cycle: Implications for HIV Susceptibility.
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Boily-Larouche, Geneviève, Lajoie, Julie, Dufault, Brenden, Omollo, Kenneth, Cheruiyot, Juliana, Njoki, Jane, Kowatsch, Monika, Kimani, Makobu, Kimani, Joshua, Oyugi, Julius, and Fowke, Keith R
- Subjects
- *
MENSTRUAL cycle , *LUTEAL phase , *HIV infections , *HIV , *MUCOUS membranes , *OVARIAN follicle , *HIV infection transmission , *BACTERIAL vaginitis , *CERVIX uteri , *COMPARATIVE studies , *INFLAMMATORY mediators , *RESEARCH methodology , *MEDICAL cooperation , *RESEARCH , *RESEARCH funding , *T cells , *VAGINA , *EVALUATION research , *IMPACT of Event Scale - Abstract
Background: Inflammation and immune activation are key factors in sexual transmission of human immunodeficiency virus (HIV). We sought to define the impact of hormonal cycling on the mucosal immune environment and HIV risk in sex workers with a natural menstrual cycle.Methods: We compared soluble mucosal immune factors and cervical mononuclear cells during hormone titer-defined phases of the menstrual cycle among 37 sex workers from Nairobi, Kenya. Systemic and mucosal samples were collected 14 days apart to distinguish the follicular and luteal phases of the menstrual cycle, and phases were confirmed by hormone measurements. Vaginal concentrations of 19 immune modulators and cervical T-cell activation markers were measured.Results: The follicular phase signature was characterized by an elevated CCL2 level, decreased interleukin 1α and interleukin 1β cervical concentrations, and a significant increase in the proportion of CD4+ T cells that expressed CD69. The genital concentration of CCL2 was the best marker to distinguish the follicular from the luteal phase in univariate and multivariate analyses and remained independent of elevated genital inflammation and bacterial vaginosis.Conclusion: The follicular phase of the menstrual cycle was associated with an elevated CCL2 level and retention of resident memory CD4+ T cells, which has implications for increased susceptibility to HIV infection. [ABSTRACT FROM AUTHOR]- Published
- 2019
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29. The Evolving Facets of Bacterial Vaginosis: Implications for HIV Transmission.
- Author
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McKinnon, Lyle R., Achilles, Sharon L., Bradshaw, Catriona S., Burgener, Adam, Crucitti, Tania, Fredricks, David N., Jaspan, Heather B., Kaul, Rupert, Kaushic, Charu, Klatt, Nichole, Kwon, Douglas S., Marrazzo, Jeanne M., Masson, Lindi, McClelland, R. Scott, Ravel, Jacques, van de Wijgert, Janneke H.H.M., Vodstrcil, Lenka A., and Tachedjian, Gilda
- Abstract
Bacterial vaginosis (BV) is a common yet poorly understood vaginal condition that has become a major focus of HIV transmission and immunology research. Varied terminologies are used by clinicians and researchers to describe microbial communities that reside in the female reproductive tract (FRT), which is driven, in part, by microbial genetic and metabolic complexity, evolving diagnostic and molecular techniques, and multidisciplinary perspectives of clinicians, epidemiologists, microbiologists, and immunologists who all appreciate the scientific importance of understanding mechanisms that underlie BV. This Perspectives article aims to clarify the varied terms used to describe the cervicovaginal microbiota and its "nonoptimal" state, under the overarching term of BV. The ultimate goal is to move toward language standardization in future literature that facilitates a better understanding of the impact of BV on FRT immunology and risk of sexually transmitted infections, including HIV. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
30. Semen IgM, IgG1, and IgG3 Differentially Associate With Pro-Inflammatory Cytokines in HIV-Infected Men.
- Author
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Pillay, Thevani, Sobia, Parveen, Olivier, Abraham Jacobus, Narain, Kapil, Liebenberg, Lenine J. P., Ngcapu, Sinaye, Mhlongo, Mesuli, Passmore, Jo-Ann S., Baxter, Cheryl, and Archary, Derseree
- Subjects
HIV-positive men ,CYTOKINES ,CHEMOKINES ,SEMEN ,IMMUNOGLOBULINS - Abstract
Genital inflammation significantly increases the risk for HIV infection. The seminal environment is enriched in pro-inflammatory cytokines and chemokines. Here, we investigated the interplay between semen cytokines and humoral immunity to understand whether the characteristics of semen antibodies are associated with genital inflammation. In 36 HIV-infected and 40 HIV-uninfected mens' semen, HIV-specific antibodies (gp120, gp41, p66, and p24), immunoglobulin (Ig) subclasses, isotypes and cytokines, using multiplex assays, were measured. Semen IgG1, IgG3, and IgM were significantly higher in HIV-infected compared to HIV-uninfected men (p < 0.05). In HIV-uninfected men, pro-inflammatory cytokines IL-6, IL-8, and MCP-1 significantly correlated with IgG1 and total IgG (IgG1+IgG2+IgG3+IgG4) (both r ≥0.55; p ≤0.001). Total IgG in HIV-infected men correlated to HIV-specific antibodies in the semen irrespective of antiretroviral (ARV) use. In HIV-infected, ARV-treated men, p66 and gp41-specific antibodies were inversely correlated with IL-6 and MIP-1α (both r ≥−0.65, p ≤0.03). In HIV-infected, ARV-naïve men, p24 and gp120-specific antibodies correlated significantly with pro-inflammatory TNF-α (r ≥0.44, p ≤0.03), while p24 antibodies correlated significantly with chemokine MIP-1β (r = 0.45; p = 0.02). Local cytokines/chemokines were associated with the mucosal-specific Ig subclasses which likely effect specific antibody functions. Together, these data inform on mucosal-specific immunity that may be elicited in the male genital tract (MGT) in future vaccines and/or combination HIV prevention strategies. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
31. Patterns of pediatric and adolescent female genital inflammation in China: an eight-year retrospective study of 49,175 patients in China.
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Gao H, Zhang Y, Pan Y, Zhao M, Qi Y, Zhou M, Chan SSC, Huang S, Song P, Tang K, Sun L, and Yuan C
- Subjects
- Humans, Child, Adolescent, Female, Infant, Newborn, Infant, Child, Preschool, Retrospective Studies, China epidemiology, Escherichia coli, Hospitals, Pediatric, Genitalia, Female, Inflammation epidemiology, Genitalia
- Abstract
Background: Genital inflammation is one of the most frequent clinical complaints among girls, which was easily overlooked by the general public. This study aimed to investigate the patterns and epidemiological characteristics of pediatric and adolescent female genital inflammation in China., Methods: A retrospective observational study (2011 to 2018) was conducted among all female patients under the age of 0-18 years at the Department of Pediatric and Adolescent Gynecology of The Children's Hospital, Zhejiang University School of Medicine. Data were collected from the electronic medical records. The abnormal vaginal discharge of patient was collected for microbiological investigation by bacterial and fungal culture. Descriptive analysis was conducted to evaluate the genital inflammation pattern and epidemiological characteristics, including age, season, and type of infected pathogens., Results: A total of 49,175 patients met the eligibility criteria of genital inflammation and 16,320 patients later came to the hospital for follow-up over the study period. The number of first-visit increased gradually from 3,769 in 2011 to 10,155 in 2018. The peak age of the first visit was 0-6 years old. Non-specific vulvovaginitis, lichen sclerosis, and labial adhesion were the top three genital inflammation. Among the top five potential common pathogens of vaginal infection, the prevalence of Haemophilus influenzae cases was the highest (31.42%, 203/646), followed by Streptococcus pyogenes (27.74%, 176/646), Candida albicans (14.09%, 91/646), Escherichia coli (8.51%, 55/646), and Staphylococcus aureus (6.35%, 41/636). The specific disease categories and pathogens of genital inflammation vary by age groups and season., Conclusion: Our study summarizes the pattern of pediatric and adolescent female genital inflammation over an 8-year period in China, emphasizing the need for more public awareness, healthcare services and research in this field., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gao, Zhang, Pan, Zhao, Qi, Zhou, Chan, Huang, Song, Tang, Sun and Yuan.)
- Published
- 2023
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32. The Influence of Cervicovaginal Microbiota on Mucosal Immunity and Prophylaxis in the Battle against HIV.
- Author
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Farcasanu, Mara and Kwon, Douglas S.
- Abstract
Purpose of Review: Young women in sub-Saharan Africa bear a disproportionate burden of the global HIV epidemic. In this review, we examine how cervicovaginal microbiota modulate structural and immune defenses in the female genital tract and influence HIV susceptibility.Recent Findings: Highly diverse, anaerobic cervicovaginal microbiota prevalent in sub-Saharan African women increase HIV acquisition risk by over fourfold. These bacteria weaken the barrier properties of the vaginal mucosa and increase local inflammation and HIV target cell recruitment, creating an environment permissive to HIV. These communities also diminish the prophylactic efficacy of topical tenofovir and therefore may modulate both biological susceptibility to HIV and the effectiveness of pre-exposure prophylaxis (PrEP).Summary: Cervicovaginal bacteria influence multiple reproductive health outcomes, including HIV acquisition. High-diversity, low
Lactobacillus abundance cervicovaginal communities prevalent in many regions with high HIV incidence are associated with increased HIV susceptibility. A better understanding of the host-microbial interactions mediating this risk is important to reduce HIV infections, particularly among women living in sub-Saharan Africa. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
33. Penile Immune Activation and Risk of HIV Shedding: A Prospective Cohort Study.
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Patel, Eshan U., Kirkpatrick, Allison R., Grabowski, Mary Kate, Kigozi, Godfrey, Gray, Ronald H., Prodger, Jessica L., Redd, Andrew D., Nalugoda, Fred, Serwadda, David, Wawer, Maria J., Quinn, Thomas C., and Tobian, Aaron A. R.
- Subjects
- *
PENIS physiology , *IMMUNE response , *HIV infection transmission , *SEXUALLY transmitted diseases , *CIRCUMCISION , *HIV infection risk factors - Abstract
Background. Genital immune activation is suspected to modulate local human immunodeficiency virus (HIV) RNA levels and the risk of sexual HIV transmission. Methods. A prospective, observational cohort study of 221 HIV-infected men undergoing male circumcision (MC) was conducted in Rakai, Uganda. Penile lavage samples collected from the coronal sulcus at baseline and 4 weekly visits after MC were assayed for pro-inflammatory cytokines and HIV RNA. The main analysis was limited to 175 men with detectable HIV plasma viral load (VL > 400 copies/mL; n = 808 visits). The primary exposures of interest were individual and total cytokine detection at the previous postoperative visit. Adjusted prevalence risk ratios (adjPRR) of detectable HIV shedding (VL > 40 copies/mL) were estimated by Poisson regression models with generalized estimating equations and robust variance estimators and included adjustment for plasma HIV VL. Findings. Among men with a detectable plasma VL, penile HIV shedding was detected at 136 visits (16.8%). Detectable interleukin (IL)-1β (adjPRR = 2.14; 95% confidence interval (CI) = 1.02-4.48), IL-6 (adjPRR = 2.24; 95% CI = 1.28-3.90), IL-8 (adjPRR = 2.42; 95% CI = 1.15-5.08), IL-10 (adjPRR = 2.51; 95% CI = 1.67-3.80), and IL-13 (adjPRR = 1.87; 95% CI = 1.15-3.03) were associated with penile HIV shedding at the subsequent visit. Men with 2-4 (adjPRR = 2.36; 95% CI = 1.08-5.14) and 5-7 (adjPRR = 3.00; 95% CI = 1.28-7.01) detectable cytokines had a greater likelihood of detectable penile HIV shedding at the subsequent visit, compared to men with = 1 detectable cytokine. The total number of detectable cytokines was also associated with a higher penile log10 HIV VL at the subsequent visit among HIV shedders. Interpretation. Pro-inflammatory cytokine production had a dose-dependent and temporal association with penile HIV shedding, suggesting that genital immune activation may increase the risk of sexual HIV transmission by driving local HIV replication. [ABSTRACT FROM AUTHOR]
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- 2017
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34. Immunometabolic Analysis of Mobiluncus mulieris and Eggerthella sp. Reveals Novel Insights Into Their Pathogenic Contributions to the Hallmarks of Bacterial Vaginosis
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Ross McKenzie, Jason D. Maarsingh, Paweł Łaniewski, and Melissa M. Herbst-Kralovetz
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Microbiology (medical) ,Mobiluncus ,vaginal dysbiosis ,Microbiota ,genital inflammation ,Immunology ,Infant, Newborn ,vaginal microbiome ,Vaginosis, Bacterial ,global metabolic and regulatory networks ,Microbiology ,QR1-502 ,cervical epithelial barrier ,Cellular and Infection Microbiology ,Infectious Diseases ,biogenic amines (BAs) ,women’s health ,Pregnancy ,Vagina ,Humans ,Premature Birth ,Female ,organotypic 3D culture ,Original Research - Abstract
The cervicovaginal microbiome plays an important role in protecting women from dysbiosis and infection caused by pathogenic microorganisms. In healthy reproductive-age women the cervicovaginal microbiome is predominantly colonized by protective Lactobacillus spp. The loss of these protective bacteria leads to colonization of the cervicovaginal microenvironment by pathogenic microorganisms resulting in dysbiosis and bacterial vaginosis (BV). Mobiluncus mulieris and Eggerthella sp. are two of the many anaerobes that can contribute to BV, a condition associated with multiple adverse obstetric and gynecological outcomes. M. mulieris has been linked to high Nugent scores (relating to BV morphotypes) and preterm birth (PTB), whilst some bacterial members of the Eggerthellaceae family are highly prevalent in BV, and identified in ~85-95% of cases. The functional impact of M. mulieris and Eggerthella sp. in BV is still poorly understood. To determine the individual immunometabolic contributions of Eggerthella sp. and M. mulieris within the cervicovaginal microenvironment, we utilized our well-characterized human three-dimensional (3-D) cervical epithelial cell model in combination with multiplex immunoassays and global untargeted metabolomics approaches to identify key immune mediators and metabolites related to M. mulieris and Eggerthella sp. infections. We found that infection with M. mulieris significantly elevated multiple proinflammatory markers (IL-6, IL-8, TNF-α and MCP-1) and altered metabolites related to energy metabolism (nicotinamide and succinate) and oxidative stress (cysteinylglycine, cysteinylglycine disulfide and 2-hydroxygluatrate). Eggerthella sp. infection significantly elevated multiple sphingolipids and glycerolipids related to epithelial barrier function, and biogenic amines (putrescine and cadaverine) associated with elevated vaginal pH, vaginal amine odor and vaginal discharge. Our study elucidated that M. mulieris elevated multiple proinflammatory markers relating to PTB and STI acquisition, as well as altered energy metabolism and oxidative stress, whilst Eggerthella sp. upregulated multiple biogenic amines associated with the clinical diagnostic criteria of BV. Future studies are needed to evaluate how these bacteria interact with other BV-associated bacteria within the cervicovaginal microenvironment.
- Published
- 2021
35. Hyaluronic acid is a negative regulator of mucosal fibroblast-mediated enhancement of HIV infection
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Martin R Jakobsen, Warner C. Greene, Guorui Xie, Anders Laustsen, Jason Neidleman, Satish K. Pillai, Johanne H Egedal, Thomas A. Packard, Nadia R. Roan, and Konstantinos Georgiou
- Subjects
0301 basic medicine ,CD4-Positive T-Lymphocytes ,Human immunodeficiency virus (HIV) ,HIV Infections ,medicine.disease_cause ,Medical and Health Sciences ,Extracellular matrix ,ACTIVATION ,chemistry.chemical_compound ,Foreskin ,0302 clinical medicine ,Hyaluronic acid ,Immunology and Allergy ,2.1 Biological and endogenous factors ,Hyaluronic Acid ,Aetiology ,RISK ,DEATH ,IMMUNODEFICIENCY-VIRUS TYPE-1 ,Biological Sciences ,Extracellular Matrix ,RECEPTORS ,medicine.anatomical_structure ,Infectious Diseases ,Gene Knockdown Techniques ,Host-Pathogen Interactions ,HIV/AIDS ,Disease Susceptibility ,medicine.symptom ,Infection ,GENITAL INFLAMMATION ,Sexual transmission ,ICAM-1 ,TRANSMISSION ,Immunology ,Inflammation ,Biology ,Article ,Microbiology ,03 medical and health sciences ,CIAP2 ,Clinical Research ,medicine ,Humans ,Fibroblast ,Gene ,Mucous Membrane ,ACQUISITION ,Fibroblasts ,030104 developmental biology ,chemistry ,Gene Expression Regulation ,HIV-1 ,Hyaluronan Synthases ,030217 neurology & neurosurgery ,Biomarkers - Abstract
The majority of HIV infections are established through the genital or rectal mucosa. Fibroblasts are abundant in these tissues, and although not susceptible to infection, can potently enhance HIV infection of CD4+ T cells. Hyaluronic acid (HA) is a major component of the extracellular matrix of fibroblasts, and its levels are influenced by the inflammatory state of the tissue. Since inflammation is known to facilitate HIV sexual transmission, we investigated the role of HA in genital mucosal fibroblast-mediated enhancement of HIV infection. Depletion of HA by CRISPR-Cas9 in primary foreskin fibroblasts augmented the ability of the fibroblasts to increase HIV infection of CD4+ T cells. This amplified enhancement required direct contact between the fibroblasts and CD4+ T cells, and could be attributed to both increased rates of trans-infection and the increased ability of HA-deficient fibroblasts to push CD4+ T cells into a state of higher permissivity to infection. This HIV-permissive state was characterized by differential expression of genes associated with regulation of cell metabolism and death. Our results suggest that conditions resulting in diminished cell-surface HA on fibroblasts, such as genital inflammation, can promote HIV transmission by conditioning CD4+ T cells toward a state more vulnerable to infection by HIV.
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- 2021
36. The Evolving Facets of Bacterial Vaginosis: Implications for HIV Transmission
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Nichole R. Klatt, Jacques Ravel, Catriona S. Bradshaw, Sharon L. Achilles, Gilda Tachedjian, Janneke van de Wijgert, Rupert Kaul, Adam Burgener, Lindi Masson, Jeanne M. Marrazzo, Lyle R. McKinnon, Charu Kaushic, David N. Fredricks, Tania Crucitti, Douglas S. Kwon, R. Scott McClelland, Lenka A. Vodstrcil, and Heather B. Jaspan
- Subjects
Adult ,Risk ,0301 basic medicine ,medicine.medical_specialty ,Immunology ,Human immunodeficiency virus (HIV) ,HIV Infections ,medicine.disease_cause ,03 medical and health sciences ,0302 clinical medicine ,Cytokines metabolism ,Clinical Perspective ,RNA, Ribosomal, 16S ,Terminology as Topic ,Virology ,Disease Transmission, Infectious ,Journal Article ,medicine ,Humans ,030212 general & internal medicine ,Intensive care medicine ,Hiv transmission ,vaginal microbiota ,Inflammation ,business.industry ,Microbiota ,female reproductive tract ,genital inflammation ,High-Throughput Nucleotide Sequencing ,HIV ,Vaginosis, Bacterial ,medicine.disease ,3. Good health ,HIV transmission ,Lactobacillus ,030104 developmental biology ,Infectious Diseases ,Vagina ,Cytokines ,Female ,Disease Susceptibility ,Bacterial vaginosis ,Female Reproductive Tract ,business ,bacterial vaginosis - Abstract
Bacterial vaginosis (BV) is a common yet poorly understood vaginal condition that has become a major focus of HIV transmission and immunology research. Varied terminologies are used by clinicians and researchers to describe microbial communities that reside in the female reproductive tract (FRT), which is driven, in part, by microbial genetic and metabolic complexity, evolving diagnostic and molecular techniques, and multidisciplinary perspectives of clinicians, epidemiologists, microbiologists, and immunologists who all appreciate the scientific importance of understanding mechanisms that underlie BV. This Perspectives article aims to clarify the varied terms used to describe the cervicovaginal microbiota and its “nonoptimal” state, under the overarching term of BV. The ultimate goal is to move toward language standardization in future literature that facilitates a better understanding of the impact of BV on FRT immunology and risk of sexually transmitted infections, including HIV.
- Published
- 2019
37. The efficacy and mechanism of acupuncture in the treatment of male infertility: A literature review.
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Feng J, He H, Wang Y, Zhang X, Zhang X, Zhang T, Zhu M, Wu X, and Zhang Y
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- Male, Humans, Spermatozoa, Semen, Infertility, Male therapy, Infertility, Male etiology, Varicocele therapy, Varicocele surgery, Acupuncture Therapy adverse effects
- Abstract
Fertility, a social, cultural, and medical issue, has aroused public attention because of its potential to predict future health. In recent years, the incidence of male infertility has increased significantly, and various risk factors, such as congenital factors, acquired factors, and idiopathic factors, have led to this situation. Male infertility causes substantial psychological and social distress in patients. With the implementation of the two-child policy, male infertility has brought enormous psychological and social pressure and huge economic burden to patients and the healthcare system. This has attracted the attention of not only men of childbearing age but also many male experts. The conventional therapeutic approaches for treating male infertility, including drugs, varicocele surgery, intrauterine insemination, in vitro fertilization, and intracytoplasmic sperm injection, can restore fertility to a certain extent, but their efficacy is far from satisfactory, not to mention some adverse events. Therefore, acupuncture has been chosen by many men to treat their infertility and produced significant effects. In the present paper, the efficacy and mechanism of acupuncture in the treatment of male infertility were analyzed from different perspectives such as regulating hormone secretion, reducing inflammation, and improving semen parameters. The existing literature shows that acupuncture can effectively treat male infertility., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Feng, He, Wang, Zhang, Zhang, Zhang, Zhu, Wu and Zhang.)
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- 2022
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38. Characterization of the Genital Mucosa Immune Profile to Distinguish Phases of the Menstrual Cycle: Implications for HIV Susceptibility
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Julius Oyugi, Makobu Kimani, Kenneth Omollo, Keith R. Fowke, Jane Njoki, Geneviève Boily-Larouche, Joshua Kimani, Brenden Dufault, Juliana Cheruiyot, Julie Lajoie, and Monika M. Kowatsch
- Subjects
CD4-Positive T-Lymphocytes ,0301 basic medicine ,Sexual transmission ,media_common.quotation_subject ,Genital inflammation ,Physiology ,HIV Infections ,Inflammation ,Cervix Uteri ,Luteal phase ,menstrual cycle ,immune activation ,Major Articles and Brief Reports ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Follicular phase ,medicine ,Humans ,Immunology and Allergy ,030212 general & internal medicine ,Chemokine CCL2 ,Menstrual cycle ,media_common ,Sex Workers ,business.industry ,HIV ,Vaginosis, Bacterial ,medicine.disease ,Kenya ,3. Good health ,030104 developmental biology ,Infectious Diseases ,Vagina ,HIV/AIDS ,Female ,medicine.symptom ,Bacterial vaginosis ,business ,Biomarkers ,Hormone - Abstract
Here, we compared the impact of endogenous sexual hormones on the mucosal immune response. Our study shows that the follicular phase of the menstrual cycle was associated with elevated level of cervical CCL2 and retention of resident memory CD4+ T cells., Background Inflammation and immune activation are key factors in sexual transmission of human immunodeficiency virus (HIV). We sought to define the impact of hormonal cycling on the mucosal immune environment and HIV risk in sex workers with a natural menstrual cycle. Methods We compared soluble mucosal immune factors and cervical mononuclear cells during hormone titer–defined phases of the menstrual cycle among 37 sex workers from Nairobi, Kenya. Systemic and mucosal samples were collected 14 days apart to distinguish the follicular and luteal phases of the menstrual cycle, and phases were confirmed by hormone measurements. Vaginal concentrations of 19 immune modulators and cervical T-cell activation markers were measured. Results The follicular phase signature was characterized by an elevated CCL2 level, decreased interleukin 1α and interleukin 1β cervical concentrations, and a significant increase in the proportion of CD4+ T cells that expressed CD69. The genital concentration of CCL2 was the best marker to distinguish the follicular from the luteal phase in univariate and multivariate analyses and remained independent of elevated genital inflammation and bacterial vaginosis. Conclusion The follicular phase of the menstrual cycle was associated with an elevated CCL2 level and retention of resident memory CD4+ T cells, which has implications for increased susceptibility to HIV infection.
- Published
- 2018
39. Improving the relaxing effect of terbutaline with phosphodiesterase inhibitors: Studies on pregnant rat uteri in vitro
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Klukovits, Anna, Verli, Judit, Falkay, George, and Gáspár, Róbert
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- *
PHOSPHODIESTERASES , *ENZYME inhibitors , *ADENOSINE monophosphate , *INFLAMMATION , *THEOPHYLLINE , *DIURETICS - Abstract
Abstract: Aims: Previous results by our group showed that the in vitro uterus-relaxing potency of β2-adrenergic receptor (β2-AR) agonists and uterine cAMP accumulation are enhanced in case of visceral inflammation. Our aim was to study the effects of the non-selective phosphodiesterase (PDE) inhibitor theophylline and the selective PDE4 inhibitor rolipram on the uteri of intact late-pregnant female rats (on days 20 and 22 of pregnancy) and of pregnant rats treated with lipopolysaccharide (LPS) to evoke preterm labor (on day 20). Main methods: The effects of theophylline and rolipram alone and of rolipram with terbutaline were investigated in isolated organ system. Contractions were evoked with KCl. The forskolin- and terbutaline-stimulated cAMP accumulations were determined by enzyme immunoassay, with or without rolipram. Key findings: The maximum uterus-relaxing effects of theophylline and rolipram decreased significantly (p <0.05) with the progression of pregnancy in intact rats. The most pronounced effect of rolipram was detected in rats challenged with LPS on day 20. Rolipram increased the in vitro effect of terbutaline both in intact and in LPS-treated rats. In the presence of rolipram, the forskolin- and terbutaline-stimulated cAMP accumulations were higher in LPS-treated than in intact rats. Significance: The previous findings led us to conclude that the combined administration of PDE4 inhibitors with β2-agonists is of therapeutic value for the inhibition for uterine contractions, especially in the case of genital inflammation, which often triggers preterm birth. Combination therapy in general is associated with lesser side-effects, as a consequence of lower effective doses of each drug. [ABSTRACT FROM AUTHOR]
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- 2010
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40. The use of PSA as a biomarker of recent semen exposure in female reproductive health studies.
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Mngomezulu, Khanyisile, Mzobe, Gugulethu, Mtshali, Andile, Baxter, Cheryl, and Ngcapu, Sinaye
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- *
BIOMARKERS , *PROSTATE-specific antigen , *SEMEN , *GENITALIA , *HUMAN sexuality - Abstract
• Semen exposure may influence the inflammatory response and alter microbial composition of the female genital tract. • Semen exposure may be a significant confounder that the majority of studies have failed to control for in their analysis. • PSA has been used as a biomarker of recent semen exposure. • PSA could be used to reflect high-risk sexual behavior and verify recent semen exposure. Semen contains potent soluble proteins, bacteria, viruses, activated immune cells as well as anti- and pro-inflammatory cytokines that may influence the inflammatory response and alter microbial composition of the female genital tract. The presence of semen in the female genital mucosa may be a significant confounder that most studies have failed to control for in their analysis. Prostate-specific antigen (PSA), a protein secreted by the prostate into the urethra during ejaculation, is a well-established biomarker of semen exposure. Several studies have demonstrated discordance between self-reports of sexual behavior and the presence of PSA. Recent semen exposure has been shown to promote pro-inflammatory responses, stimulate the recruitment of activated immune cells and decrease Lactobacilli abundance in the female genital mucosa. As a result, it is important to understand the concordance between self-reported consistent condom use and the presence of semen biomarkers. Furthermore, to ensure that the interpretation of data in clinical studies of the immunological and microbial environment in the female genital mucosa are accurate, it is essential to establish whether semen is present in the vaginal fluid. This review explores the impact of semen exposure on the mucosal microenvironment and assesses the use of the PSA as an objective biomarker of semen exposure to reduce reliance on self-reported sexual intercourse. [ABSTRACT FROM AUTHOR]
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- 2021
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41. Vaginal dysbiosis associated-bacteria Megasphaera elsdenii and Prevotella timonensis induce immune activation via dendritic cells
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van Teijlingen, Nienke H, Helgers, Leanne C, Zijlstra-Willems, Esther M, van Hamme, John L, Ribeiro, Carla M S, Strijbis, Karin, Geijtenbeek, Teunis B H, LS Infectiebiologie (Bacteriologie), dI&I I&I-2, Graduate School, ARD - Amsterdam Reproduction and Development, AII - Infectious diseases, Experimental Immunology, Infectious diseases, LS Infectiebiologie (Bacteriologie), and dI&I I&I-2
- Subjects
0301 basic medicine ,Immunology ,Pro-inflammatory cytokines ,Primary Cell Culture ,Prevotella ,Genital inflammation ,Inflammation ,maturation markers ,Vaginal microbiome ,Proinflammatory cytokine ,Microbiology ,03 medical and health sciences ,T helper cells ,0302 clinical medicine ,medicine ,Immunology and Allergy ,Humans ,dendritic cells ,Cells, Cultured ,030219 obstetrics & reproductive medicine ,Lactobacillus crispatus ,biology ,Maturation markers ,genital inflammation ,vaginal microbiome ,Obstetrics and Gynecology ,Dendritic Cells ,Vaginosis, Bacterial ,medicine.disease ,biology.organism_classification ,3. Good health ,030104 developmental biology ,Reproductive Medicine ,Megasphaera elsdenii ,Vagina ,Leukocytes, Mononuclear ,Prevotella timonensis ,Cytokines ,Dysbiosis ,Female ,Anaerobic bacteria ,medicine.symptom ,Bacterial vaginosis ,Inflammation Mediators ,Bacteria - Abstract
Dysbiosis of the vaginal microbiome as a result of overgrowth of anaerobic bacteria leads to bacterial vaginosis (BV) which is associated with increased inflammation in the genital mucosa. Moreover, BV increases susceptibility to sexual transmitted infections (STIs) and is associated with adverse pregnancy outcomes. It remains unclear how specific vaginal aerobic and anaerobic bacteria affect health and disease. We selected different vaginal bacteria ranging from true commensals to species associated with dysbiosis and investigated their effects on activation of dendritic cells (DCs). Commensal Lactobacilli crispatus did not induce DC maturation nor led to production of pro-inflammatory cytokines. In contrast, BV-associated bacteria Megasphaera elsdenii and Prevotella timonensis induced DC maturation and increased levels of pro-inflammatory cytokines. Notably, DCs stimulated with Prevotella timonensis suppressed Th2 responses and induced Th1 skewing, typically associated with preterm birth. In contrast, Lactobacillus crispatus and Megasphaera elsdenii did not affect Th cell polarization. These results strongly indicate that the interaction of vaginal bacteria with mucosal DCs determines mucosal inflammation and we have identified the anaerobic bacterium Prevotella timonensis as a strong inducer of inflammatory responses. Specifically targeting these inflammation-inducing bacteria might be a therapeutic strategy to prevent BV and associated risks in STI susceptibility and preterm birth.
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- 2019
42. The genital tract and rectal microbiomes: their role in HIV susceptibility and prevention in women
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Jo-Ann S. Passmore, Brent L. Williams, Lyle R. McKinnon, Cheryl Baxter, and Salim S. Abdool Karim
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ved/biology.organism_classification_rank.species ,HIV prevention ,Reviews ,HIV Infections ,Review ,Prevotellaceae ,medicine.disease_cause ,Prevotella bivia ,tenofovir gel ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Gardnerella vaginalis ,Humans ,Sex organ ,030212 general & internal medicine ,Microbiome ,Genitalia ,Reproductive health ,030505 public health ,biology ,Bacteria ,business.industry ,ved/biology ,genital inflammation ,Public Health, Environmental and Occupational Health ,Rectum ,vaginal microbiome ,medicine.disease ,biology.organism_classification ,Gastrointestinal Microbiome ,Infectious Diseases ,medicine.anatomical_structure ,Immunology ,Vagina ,Female ,women ,Bacterial vaginosis ,0305 other medical science ,business ,rectal microbiome - Abstract
Introduction Young women in sub‐Saharan Africa are disproportionately affected by HIV, accounting for 25% of all new infections in 2017. Several behavioural and biological factors are known to impact a young woman's vulnerability for acquiring HIV. One key, but lesser understood, biological factor impacting vulnerability is the vaginal microbiome. This review describes the vaginal microbiome and examines its alterations, its influence on HIV acquisition as well as the efficacy of HIV prevention technologies, the role of the rectal microbiome in HIV acquisition, advances in technologies to study the microbiome and some future research directions. Discussion Although the composition of each woman's vaginal microbiome is unique, a microbiome dominated by Lactobacillus species is generally associated with a “healthy” vagina. Disturbances in the vaginal microbiota, characterized by a shift from a low‐diversity, Lactobacillus‐dominant state to a high‐diversity non‐Lactobacillus‐dominant state, have been shown to be associated with a range of adverse reproductive health outcomes, including increasing the risk of genital inflammation and HIV acquisition. Gardnerella vaginalis and Prevotella bivia have been shown to contribute to both HIV risk and genital inflammation. In addition to impacting HIV risk, the composition of the vaginal microbiome affects the vaginal concentrations of some antiretroviral drugs, particularly those administered intravaginally, and thereby their efficacy as pre‐exposure prophylaxis (PrEP) for HIV prevention. Although the role of rectal microbiota in HIV acquisition in women is less well understood, the composition of this compartment's microbiome, particularly the presence of species of bacteria from the Prevotellaceae family likely contribute to HIV acquisition. Advances in technologies have facilitated the study of the genital microbiome's structure and function. While next‐generation sequencing advanced knowledge of the diversity and complexity of the vaginal microbiome, the emerging field of metaproteomics, which provides important information on vaginal bacterial community structure, diversity and function, is further shedding light on functionality of the vaginal microbiome and its relationship with bacterial vaginosis (BV), as well as antiretroviral PrEP efficacy. Conclusions A better understanding of the composition, structure and function of the microbiome is needed to identify opportunities to alter the vaginal microbiome and prevent BV and reduce the risk of HIV acquisition.
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- 2019
43. Persistent, Asymptomatic Colonization with Candida is Associated with Elevated Frequencies of Highly Activated Cervical Th17-Like Cells and Related Cytokines in the Reproductive Tract of South African Adolescents.
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Happel AU, Gasper M, Balle C, Konstantinus I, Gamieldien H, Dabee S, Gill K, Bekker LG, Passmore JS, and Jaspan HB
- Subjects
- Adolescent, Asymptomatic Infections, Candida, Dysbiosis, Female, Humans, Inflammation, RNA, Ribosomal, 16S, South Africa epidemiology, Th17 Cells, Vagina microbiology, Young Adult, Cytokines, HIV Infections
- Abstract
Cervicovaginal inflammation, nonoptimal microbiota, T-cell activation, and hormonal contraceptives may increase HIV risk, yet associations between these factors and subclinical Candida colonization or hyphae are unknown. We collected cervicovaginal samples from 94 South African adolescents, aged 15 to 19 years, who were randomized to injectable norethisterone enanthate (Net-En), an etonorgesterol/ethinyl estradiol vaginal ring (NuvaRing), or oral contraceptives in the UChoose trial (NCT02404038) at baseline and 16 weeks post-randomization. We assessed cervicovaginal samples for subclinical Candida colonization (by quantitative PCR [qPCR]), hyphae (by Gram stain), microbiota composition (by 16S rRNA gene sequencing), cytokine concentrations (by Luminex), and cervical T-cell phenotypes and activation (by multiparameter flow cytometry). While hormonal contraceptive type did not influence incidence of Candida colonization or hyphae, hyphae presence was associated with significantly elevated concentrations of IL-22, IL-17A and IL-17F, all produced by Th17 cells, but not of other cytokines, such as IL-1β or IL-6, after adjustment for confounders. Subclinical Candida colonization was associated with reduced frequencies of Th17-like cells and elevated frequencies of CCR6-CCR10 T cells. Women with Candida hyphae were less likely to have bacterial vaginosis (BV). Persistent, subclinical colonization with Candida over 16 weeks was associated with significant increases in Th17-related cytokine concentrations and highly activated Th17-like and CCR6-CCR10 T-cell frequencies. These data suggest that vaginal Candida colonization and hyphae increase Th17-related cytokines, but not overall female genital tract inflammation in Sub-Saharan African adolescents. Persistent Candida colonization, even when asymptomatic, may increase Th17 cell frequencies and related cytokines and thereby could subsequently increase HIV risk, although the causal relationship requires confirmation. IMPORTANCE Sub-Saharan African female adolescents are globally at the highest risk of HIV acquisition, and genital inflammation, microbial dysbiosis, and cervical HIV target cell activation are thought to contribute to this risk. Previously, the relationship between these mucosal factors and subclinical vaginal Candida colonization or hyphae has not been described, and the role of HIV-susceptible Th17 cells in mediating anti- Candida immunity in the human female genital tract has not been clearly established. We show that presence of yeast hyphae was associated with increases in Th17 cell-related cytokines and the absence of microbial dysbiosis, and that persistent Candida colonization resulted in significant increases in Th17-related cytokines and highly activated Th17-like cell frequencies. Our results suggest that Th17 cells are important for anti- Candida immunity in the human female genital tract and that prolonged vaginal Candida colonization may contribute to increased HIV risk in Sub-Saharan African adolescents by increasing HIV target cell frequencies and activation.
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- 2022
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44. Cervicovaginal DNA Virome Alterations Are Associated with Genital Inflammation and Microbiota Composition.
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Kaelin EA, Skidmore PT, Łaniewski P, Holland LA, Chase DM, Herbst-Kralovetz MM, and Lim ES
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- Female, Humans, Virome, Pilot Projects, Cervix Uteri microbiology, Inflammation, DNA, Tumor Microenvironment, Uterine Cervical Neoplasms, Papillomavirus Infections microbiology, Microbiota, Bacteriophages
- Abstract
While the link between the cervicovaginal bacterial microbiome, human papillomavirus (HPV) infection, and cervical cancer is recognized (P. Łaniewski, D. Barnes, A. Goulder, H. Cui, et al., Sci. Rep. 8:7593, 2018, http://dx.doi.org/10.1038/s41598-018-25879-7; A. Mitra, D. A. MacIntyre, Y. S. Lee, A. Smith, et al., Sci. Rep. 5:16865, 2015, http://dx.doi.org/10.1038/srep16865; A. Mitra, D. A. MacIntyre, J. R. Marchesi, Y. S. Lee, et al., Microbiome 4:58, 2016, http://dx.doi.org/10.1186/s40168-016-0203-0; J. Norenhag, J. Du, M. Olovsson, H. Verstraelen, et al., BJOG, 127:171-180, 2020, http://dx.doi.org/10.1111/1471-0528.15854; E. O. Dareng, B. Ma, A. O. Famooto, S. N. Adebamowo, et al., Epidemiol. Infect. 144:123-137, 2016, http://dx.doi.org/10.1017/S0950268815000965; A. Audirac-Chalifour, K. Torres-Poveda, M. Bahena-Roman, J. Tellez-Sosa et al., PLoS One 11:e0153274, 2016, http://dx.doi.org/10.1371/journal.pone.0153274; M. Di Paola, C. Sani, A. M. Clemente, A. Iossa, et al., Sci. Rep. 7:10200, 2017, http://dx.doi.org/10.1038/s41598-017-09842-6), the role of the cervicovaginal virome remains poorly understood. In this pilot study, we conducted metagenomic next-generation sequencing of cervicovaginal lavage specimens to investigate the relationship between the cervicovaginal DNA virome, bacterial microbiome, genital inflammation, and HPV infection. Specific virome alterations were associated with features of the local microenvironment related to HPV persistence and progression to cervical cancer. Cervicovaginal viromes clustered distinctly by genital inflammation state. Genital inflammation was associated with decreased virome richness and alpha diversity and an increased abundance of Anelloviridae species from the genus Alphatorquevirus . Lactobacillus bacteriophages were closely associated with increased Lactobacillus abundance, consistent with phage-host relationships. Interestingly, bacteria-bacteriophage transkingdom interactions were linked to genital inflammation and showed specific interactions with bacterial vaginosis-associated bacteria, including Gardnerella, Prevotella, and Sneathia . Taken together, our results reveal prominent virome interactions with features of the cervicovaginal microenvironment that are associated with HPV and cervical cancer. These findings expand our understanding of the cervicovaginal host-microbiome interactions in women's health. IMPORTANCE HPV infection is an established risk factor for cervical cancer. However, more broadly, the role of the cervicovaginal virome in cervical cancer progression is not well understood. Here, we identified cervicovaginal DNA virome alterations associated with local microenvironment factors (vaginal microbiota and genital inflammation) that influence HPV persistence and progression to cervical cancer. These findings indicate that the cervicovaginal virome plays an important role in women's health.
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- 2022
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45. Etiopathogenesis of reproductive tract infections and the emerging role of bitter taste receptors: A scoping review
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Abraham Jeremiah, Senol Dane, Vladimir A. Pereverzev, Menizibeya O. Welcome, and Dennis O Allagoa
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Infertility ,General Veterinary ,Reproductive tract ,Obstetrics and Gynecology ,Plant Science ,Biology ,medicine.disease ,infection ,genital inflammation ,reproduction ,reproductive tract infections ,bitter taste receptor ,etiopathogenesis ,cytokines ,Proinflammatory cytokine ,Reproductive Medicine ,Immunology ,Tissue damage ,medicine ,Medicine ,Animal Science and Zoology ,Neonatal death ,Bitter taste receptors ,Receptor ,Preterm delivery - Abstract
Reproductive tract infections pose an immense public health concern worldwide as over 600 million new cases are recorded annually along with several complications, including infertility, ectopic pregnancy, preterm delivery, and neonatal death. Despite improved understanding of the mechanisms of pathogenic invasion, the etiopathogenesis of reproductive tract infections is yet to be completely understood. Recent data has suggested a critical role of bitter taste receptors of the reproductive tract in etiopathogenesis of reproductive tract infections. Here, we review the literature on current etiopathogenesis of reproductive tract infections and the role of bitter taste receptors of the reproductive tract in etiopathogenesis of reproductive tract infections. Emerging evidence suggests a critical role of microbiota disorder of the reproductive tract in reproductive tract infections. Several bacterial, protozoan parasitic, helminthic parasitic and viral pathogens have been identified as causative agents of reproductive tract infections. These pathogens subvert host defenses and activate specific architectural units of the uroepithelium such as Toll-like receptors, which recognize conserved motifs on the pathogens. The activated Toll-like receptors mediate downstream signaling, stimulating nuclear factor-κB, which in turn activates the production of proinflammatory cytokines. This pathway is also associated with recruitment of immunocytes to the site of aggression and release of proteinases, which drive tissue damage in the reproductive tract. Defects in detection of pathogenic components by the bitter taste receptors of the reproductive tract may play a critical role in the etiopathogenesis of reproductive tract infections. This review provides important information for identification of novel frontiers for the treatment of reproductive tract infections.
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- 2021
46. Undetected anogenital sexually transmitted infections among young adults living with HIV and receiving antiretroviral therapy: Implications for HIV treatment as prevention.
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Kalichman SC, Eaton LA, and Kalichman MO
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- Adult, Homosexuality, Male, Humans, Male, Sexual Behavior, Sexual Partners, Young Adult, Chlamydia Infections, Gonorrhea, HIV Infections complications, HIV Infections diagnosis, HIV Infections drug therapy, Sexually Transmitted Diseases diagnosis, Sexually Transmitted Diseases epidemiology, Sexually Transmitted Diseases prevention & control, Substance-Related Disorders
- Abstract
Undetected sexually transmitted infections (STIs) pose health threats to people living with HIV and when combined with uncontrolled HIV can amplify HIV transmission. The current study screened 174 self-identified men under age 36 living with HIV and receiving antiretroviral therapy (ART) for urethral and rectal incident chlamydia and gonorrhea infections. Participants were also screened for biomarkers indicating alcohol and other drug use, subclinical genital inflammation, and HIV viral load. ART adherence and sexual behaviors were also assessed prospectively over 1 month. Results detected an undiagnosed STI in 32 (18%) individuals. Participants with a previously undetected STI had significantly greater HIV viremia than those who did not have an STI after controlling for several confounding variables. Participants with an undetected STI also engaged in greater condomless anal intercourse with HIV negative and unknown status partners, including partners to whom they had not disclosed their HIV status. These findings show that undetected STI are associated with incomplete ART adherence and unsuppressed HIV, all of which are important for preventing HIV transmission.
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- 2022
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47. HIV susceptibility in women: The roles of genital inflammation, sexually transmitted infections and the genital microbiome.
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Mtshali, Andile, Ngcapu, Sinaye, Mindel, Adrian, Garrett, Nigel, and Liebenberg, Lenine
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- *
BACTERIAL vaginitis , *SEXUALLY transmitted diseases , *HIV infections , *HIV , *VIRUS diseases , *HIV infection transmission - Abstract
• Genital inflammation, sexually transmitted infections (STIs) and the genital microbiome contribute to HIV susceptibility. • Elevated inflammatory cytokine concentrations may facilitate HIV infection by recruiting and activating HIV target cells. • Disturbances in the vaginal microbiota are associated with BV and increased HIV acquisition risk. • Interventions that promote and sustain an optimal vaginal environment could benefit women's health. Given that heterosexual transmission of HIV across the genital mucosa is the most common route of infection in women, an in-depth understanding of the biological mechanisms associated with HIV risk in the female genital tract (FGT) is essential for effective control of the epidemic. Genital pro-inflammatory cytokines are well-described biological co-factors to HIV risk. Increased levels of pro-inflammatory cytokines in the FGT have been associated with a 3-fold higher-risk of acquiring HIV, presumably through involvement in barrier compromise and the recruitment of highly activated HIV target cells to the site of initial viral infection and replication. Sexually transmitted infections (STIs) and bacterial vaginosis (BV) are suggested possible contributors to genital inflammation in the FGT, and this, coupled with the relationship between genital inflammation and HIV risk, underscores the importance of effective treatment of STI and BV in the promotion of women's health. In most low- and middle-income countries, STIs are treated syndromically, a practice providing rapid treatment without identifying the infection source. However, this approach has been associated with over-diagnosis and the overuse of drugs. Further, because many women with STIs are asymptomatic, syndromic management also fails to treat a vast proportion of infected women. Although several studies have explored the role of STIs and the vaginal microbiome on genital inflammation and HIV risk, the impact of STI and BV management on genital inflammation remains poorly understood. This review aimed to collate the evidence on how BV and STI management efforts affect genital inflammation and the genital microbiome in women. [ABSTRACT FROM AUTHOR]
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- 2021
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48. Vaginal dysbiosis associated-bacteria Megasphaera elsdenii and Prevotella timonensis induce immune activation via dendritic cells.
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van Teijlingen, Nienke H., Helgers, Leanne C., Zijlstra - Willems, Esther M., van Hamme, John L., Ribeiro, Carla M.S., Strijbis, Karin, and Geijtenbeek, Teunis B.H.
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- *
DENDRITIC cells , *PREVOTELLA , *ANAEROBIC bacteria , *T helper cells , *AEROBIC bacteria , *LACTOBACILLUS plantarum , *GRAM-negative anaerobic bacteria - Abstract
• Megasphaera elsdenii and Prevotella timonensis increased expression of CD80, CD83, and CD86 on dendritic cells. • Megasphaera elsdenii and Prevotella timonensis induced production of pro-inflammatory cytokines by dendritic cells. • Prevotella timonensis -stimulated dendritic cells induced T helper 1 skewing of naïve CD4 + T cells. • Commensal Lactobacillus crispatus did not induce inflammatory immune responses in dendritic cells. Dysbiosis of the vaginal microbiome as a result of overgrowth of anaerobic bacteria leads to bacterial vaginosis (BV) which is associated with increased inflammation in the genital mucosa. Moreover, BV increases susceptibility to sexual transmitted infections (STIs) and is associated with adverse pregnancy outcomes. It remains unclear how specific vaginal aerobic and anaerobic bacteria affect health and disease. We selected different vaginal bacteria ranging from true commensals to species associated with dysbiosis and investigated their effects on activation of dendritic cells (DCs). Commensal Lactobacilli crispatus did not induce DC maturation nor led to production of pro-inflammatory cytokines. In contrast, BV-associated bacteria Megasphaera elsdenii and Prevotella timonensis induced DC maturation and increased levels of pro-inflammatory cytokines. Notably, DCs stimulated with Prevotella timonensis suppressed Th2 responses and induced Th1 skewing, typically associated with preterm birth. In contrast, Lactobacillus crispatus and Megasphaera elsdenii did not affect Th cell polarization. These results strongly indicate that the interaction of vaginal bacteria with mucosal DCs determines mucosal inflammation and we have identified the anaerobic bacterium Prevotella timonensis as a strong inducer of inflammatory responses. Specifically targeting these inflammation-inducing bacteria might be a therapeutic strategy to prevent BV and associated risks in STI susceptibility and preterm birth. [ABSTRACT FROM AUTHOR]
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- 2020
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49. Mucosal Immunity and HIV Acquisition in Women.
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de Lara LM, Parthasarathy RS, and Rodriguez-Garcia M
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Women acquire HIV through sexual transmission. Women worldwide represent half of the people living with HIV, but young women in endemic areas are disproportionally affected. Low transmission rates per sexual act in women suggest that local immune protective mechanisms in the genital tract have the potential to prevent infection. However, conditions that induce genital inflammation are known to increase the risk of HIV acquisition. The female genital tract (FGT) is divided into different anatomical compartments with distinct reproductive functions. The immune cells present in each of these compartments are specialized in balancing reproduction and protection against infections, and are the same cells that can encounter and respond to HIV. Understanding the physiological and pathological factors that influence mucosal immune cell presence, susceptibility to HIV-infection and anti-HIV immune responses in the FGT is necessary to develop preventive strategies. Here we review recent advances in our understanding of HIV infection in the human female genital tract, with an emphasis on the characterization of the mucosal cells susceptible to HIV-infection, innate immune responses and mucosal factors that increase genital inflammation and influence susceptibility to HIV acquisition in women., Competing Interests: Conflict of interested statement. Nothing declared.
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- 2021
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50. The Impact of Semen Exposure on the Immune and Microbial Environments of the Female Genital Tract.
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Jewanraj J, Ngcapu S, Osman F, Mtshali A, Singh R, Mansoor LE, Abdool Karim SS, Abdool Karim Q, Passmore JS, and Liebenberg LJP
- Abstract
Background: Semen induces an immune response at the female genital tract (FGT) to promote conception. It is also the primary vector for HIV transmission to women during condomless sex. Since genital inflammation and immune activation increase HIV susceptibility in women, semen-induced alterations at the FGT may have implications for HIV risk. Here we investigated the impact of semen exposure, as measured by self-reported condom use and Y-chromosome DNA (YcDNA) detection, on biomarkers of female genital inflammation associated with HIV acquisition. Methods: Stored genital specimens were collected biannually (mean 5 visits) from 153 HIV-negative women participating in the CAPRISA 008 tenofovir gel open-label extension trial. YcDNA was detected in cervicovaginal lavage (CVL) pellets by RT-PCR and served as a biomarker of semen exposure within 15 days of genital sampling. Protein concentrations were measured in CVL supernatants by multiplexed ELISA, and the frequency of activated CD4+CCR5+ HIV targets was assessed on cytobrush-derived specimens by flow cytometry. Common sexually transmitted infections (STIs) and bacterial vaginosis (BV)-associated bacteria were measured by PCR. Multivariable linear mixed models were used to assess the relationship between YcDNA detection and biomarkers of inflammation over time. Results: YcDNA was detected at least once in 69% (106/153) of women during the trial (median 2, range 1-5 visits), and was associated with marital status, cohabitation, the frequency of vaginal sex, and Nugent Score. YcDNA detection but not self-reported condom use was associated with elevated concentrations of several cytokines: IL-12p70, IL-10, IFN-γ, IL-13, IP-10, MIG, IL-7, PDGF-BB, SCF, VEGF, β-NGF, and biomarkers of epithelial barrier integrity: MMP-2 and TIMP-4; and with reduced concentrations of IL-18 and MIF. YcDNA detection was not associated with alterations in immune cell frequencies but was related to increased detection of P. bivia (OR = 1.970; CI 1.309-2.965; P = 0.001) at the FGT. Conclusion: YcDNA detection but not self-reported condom use was associated with alterations in cervicovaginal cytokines, BV-associated bacteria, and matrix metalloproteinases, and may have implications for HIV susceptibility in women. This study highlights the discrepancies related to self-reported condom use and the need for routine screening for biomarkers of semen exposure in studies of mucosal immunity to HIV and other STIs., (Copyright © 2020 Jewanraj, Ngcapu, Osman, Mtshali, Singh, Mansoor, Abdool Karim, Abdool Karim, Passmore and Liebenberg.)
- Published
- 2020
- Full Text
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