Bacterial vaginosis, cervical immune cells and HIV susceptibility
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PROVIDER: PRJNA693367 | ENA |
REPOSITORIES: ENA
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Project description:Bacterial vaginosis, cervical immune cells and HIV susceptibility
| PRJNA693368 | ENA
Project description:HIV-1 infections of women are mainly acquired through female reproductive tract where cervical and vaginal epithelial cells are the first line of defense. Although HIV-1 does not directly infect epithelial cells, HIV-1 obligatorily interacts with and crosses over epithelial layer to infect susceptible target cells, mainly CD4+ T cells, in the lamina propria to initiate an infection. However, the mechanism and ramification of the interaction of HIV-1 and epithelial cells in vaginal transmission of HIV-1 remain to be elucidated. We hypothesized that cervical epithelial cells are not a passive barrier, but actively respond to HIV-1 to change mucosal milieu and facilitate HIV-1 transmission. We tested this hypothesis by studying the responses of cervical epithelial cells to HIV-1 through profiling genome-wide transcription. We found 1) cervical epithelial cells actively respond to HIV-1. Five hundred forty-three transcripts/genes in cervical epithelial cells were significantly altered in expression at four hours post exposure to HIV-1, of which many relate to important signaling pathways, such as innate immune responses, pattern recognition receptors, apoptosis, biosynthesis, and energy production, 2) HIV-1 increases the expression of CXC Chemokines (IL-8, CXCL1 and CXCL3) in cervical epithelial cells. IL-8 and CXCL1 are potent chemotactic for multinuclear neutrophils (MNP), monocytes and a minority of lymphocytes, and CXCL3 is predominant chemotactic for monocytes, 3) HIV-1 increases the expression of key inflammatory enzymes-COX-1 and COX-2. COX-1 is responsible for the production of prostaglandins that are important for homeostatic functions, and COX-2 is a key enzyme to convert arachidonic acid to prostaglandins, key inflammatory mediators, and 4) the increased expression of IL-8 and COX-2 revealed using microarray analysis was mapped into the endocervical epithelial cells of macaques inoculated with inactivated SIV in vivo. Our date lead to a role model of epithelial cells in HIV-1 vaginal transmission, that is the axis of HIV-1, epithelial cells, proinflammatory molecules (IL-8, CXCL1, CXCL3, COX-1 and COX-2), cell recruitment (MNP, monocytes and T cells), and inflammation. This model implies that moderating epithelial proinflammatory response to HIV-1 may be utilized in prevention of HIV vaginal transmission.
2013-02-01 | GSE42291 | GEO
Project description:HIV-1 infections of women are mainly acquired through female reproductive tract where cervical and vaginal epithelial cells are the first line of defense. Although HIV-1 does not directly infect epithelial cells, HIV-1 obligatorily interacts with and crosses over epithelial layer to infect susceptible target cells, mainly CD4+ T cells, in the lamina propria to initiate an infection. However, the mechanism and ramification of the interaction of HIV-1 and epithelial cells in vaginal transmission of HIV-1 remain to be elucidated. We hypothesized that cervical epithelial cells are not a passive barrier, but actively respond to HIV-1 to change mucosal milieu and facilitate HIV-1 transmission. We tested this hypothesis by studying the responses of cervical epithelial cells to HIV-1 through profiling genome-wide transcription. We found 1) cervical epithelial cells actively respond to HIV-1. Five hundred forty-three transcripts/genes in cervical epithelial cells were significantly altered in expression at four hours post exposure to HIV-1, of which many relate to important signaling pathways, such as innate immune responses, pattern recognition receptors, apoptosis, biosynthesis, and energy production, 2) HIV-1 increases the expression of CXC Chemokines (IL-8, CXCL1 and CXCL3) in cervical epithelial cells. IL-8 and CXCL1 are potent chemotactic for multinuclear neutrophils (MNP), monocytes and a minority of lymphocytes, and CXCL3 is predominant chemotactic for monocytes, 3) HIV-1 increases the expression of key inflammatory enzymes-COX-1 and COX-2. COX-1 is responsible for the production of prostaglandins that are important for homeostatic functions, and COX-2 is a key enzyme to convert arachidonic acid to prostaglandins, key inflammatory mediators, and 4) the increased expression of IL-8 and COX-2 revealed using microarray analysis was mapped into the endocervical epithelial cells of macaques inoculated with inactivated SIV in vivo. Our date lead to a role model of epithelial cells in HIV-1 vaginal transmission, that is the axis of HIV-1, epithelial cells, proinflammatory molecules (IL-8, CXCL1, CXCL3, COX-1 and COX-2), cell recruitment (MNP, monocytes and T cells), and inflammation. This model implies that moderating epithelial proinflammatory response to HIV-1 may be utilized in prevention of HIV vaginal transmission. Human endocervical epithelial cell line, CRL-2615, was inoculated with HIV-1 ME1 and collected 4hrs post exposure. Biologically duplicated mRNAs were prepared after exposure.
2013-02-01 | E-GEOD-42291 | biostudies-arrayexpress
Project description:Whole transcriptome amplification of RNA purified from cervical explants (endocervix/ectocervix) cultured with different forms of HIV (free, complement opsonized and complement and antibody opsonized HIV) or mock treated for 6h or 24h.
2021-05-11 | GSE160774 | GEO
Project description:There is an ongoing debate whether sex hormones impact risk of HIV transmission. This study evaluated if serum estradiol (E2) and progesterone (P4) levels predict the ex vivo cervical tissue HIV infection, tissue immune environment and transcriptome. Cervical mucosa and peripheral blood samples were collected from subjects undergoing total hysterectomies. Tissue explants were challenged with HIV-1BaL and infection was monitored in the supernatants by HIV gag qRT-PCR. Serum E2 and P4 concentrations were measured by radioimmunoassay. Blood and tissue T cell phenotypes were characterized by flow cytometry. Tissue responses to HIV exposure were measured by Luminex. Tissue transcriptome in an unchallenged portion of mucosa was analyzed by RNAseq. We show that serum E2 concentrations inversely associated with cervical HIV-1BaL infection ex vivo and this association was independent of potential confounders (race, age, phase of the cycle, parakeratosis, metaplasia, histopathological signs of cervical inflammation, and HSV-2 status). E2 concentrations did not associate with T cell frequencies/phenotype in either tissues or blood. However, higher E2 concentrations predicted a mixed profile of pro-/anti-inflammatory genes expression and HIV-induced soluble mediators. In contrast, P4 concentrations or P4/E2 ratios did not associate with ex vivo tissue infection level, but increased P4 concentrations associated with high frequencies of a4b7+ and low LFA-1+ T cells and mainly pro-inflammatory responses to HIV. These data suggest inhibitory effect of E2 on local mucosal HIV amplification early post transmission, provide insights in the mechanism of E2-mediated anti-HIV activity and highlight P4-associated immune changes in the mucosa.
2020-06-15 | GSE100094 | GEO
Project description:Cervical cancer (CC) remains a significant public health issue in low- and middle-income countries (LMICs), especially in Western sub-Saharan Africa and Nigeria. While global CC incidence and mortality have declined, these regions continue to face high rates due to inadequate screening and the high prevalence of HIV, which increases CC risk by promoting persistent HPV infections. This study aimed to identify DNA methylation (DNAm) biomarkers for cervical intraepithelial neoplasia (CIN) and CC in HIV-positive Nigerian women and to assess their potential for clinical risk prediction. From 2018 to 2020, 538 participants were recruited from Nigerian tertiary hospitals. Cervical tissue samples were analyzed for DNAm using the Infinium MethylationEPIC BeadChip array, and HPV genotyping was conducted via next-generation sequencing. An epigenome-wide association study revealed 24 significant DNAm biomarkers associated with CIN and CC. These biomarkers showed hypermethylation in tumor suppressor genes (e.g., PRMD8), hypomethylation in oncogenes (e.g., MIR520H), and aberrant methylation in genes related to HIV/HPV infection and oncogenesis (e.g., GNB5, LMO4, FOXK2, NMT1). A machine learning-based DNAm classifier achieved 92.9% sensitivity and 88.6% specificity in predicting CC risk, with higher risk observed in adjacent normal cervical samples from CIN/CC patients and HIV/HPV co-infected women. DNAm biomarkers offer a promising approach to enhancing CC screening and early detection, particularly for HIV-positive women in LMICs. The DNAm-based model developed in this study shows potential for more accurate CC risk stratification, highlighting the need for further optimization, validation, and implementation in low-resource settings.
2024-11-01 | GSE279982 | GEO
Project description:The aim of the study was to investigate gene expression profiles of post-menopausal women receiving Premarin estrogen replacement therapy (ERT), compared to controls and to examine any correlations between the bacterial vaginosis (BV) status of the stubjects. This is the first study to use gene arrays to correlate changes in host expression to ERT and BV.
2018-04-28 | GSE113771 | GEO
Project description:Identifying the differentially expressed miRNAs in Cervical cancer patients infected with only one virus i.e. either HIV or HPV-16 and patients infected with both viruses HIV and HPV-16 with respect to their controls which is the healthy population not infected by either HIV or any HPV The miRNA array was performed using the affymetrix GeneChip® miRNA 3.0 Array (Affymetrix, Santa Clara, California, United States). The chip was processed using a commercial Affymetrix array service (GeneTech Biotechnology Limited Company, Shanghai, China). The affymetrix GeneChip® miRNA 3.0 Array contains 2,999 probe sets unique to human, mouse and rat pre-miRNA hairpin sequences, 2,216 human snoRNA and scaRNA probe sets and covers 153 organisms (19,724 probe sets). Raw data sets were extracted from all Cel files (raw intensity file) after scanning of slides. These raw data sets were separately analyzed using Expression Console and GeneSpring GX12.5 software followed by differential miRNA expression, fold change & cluster analysis.
2018-08-01 | GSE81137 | GEO
Project description:Bacterial vaginosis (BV) treatment failures or recurrences are common. To identify features associated with treatment response, we compared vaginal microbiota and host ectocervical transcriptome before and after oral metronidazole therapy. Response to metronidazole is characterized by significant changes in chemokines and related transcripts suggesting that strategies to promote these pathways may prove beneficial.
2021-05-21 | GSE174799 | GEO