HIV-exposed seronegative sex workers express high levels of regulatory T cells, low levels of T cell activation and an intact ectocervical tissue microenvironment
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE165132 | GEO | 2021/04/20
REPOSITORIES: GEO
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Project description:The Kaposi sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi sarcoma (KS), the most common HIV/AIDS-associated tumor worldwide. Transmission routes of KSHV in the general population are poorly understood. Whereas sexual transmission appears to be common in homosexual men, the evidence for heterosexual transmission is less convincing. In fact, KSHVDNA sequences have been detected in the prostate, semen, and in the female genital tract. Persistent infection with high-risk human papillomavirus (HPV) is the major risk factor and is a requirement for the development of cervical cancer. However, it remains unknown the interaction between KSHV and HPV, and the contribution of KSHV to cervical cancer development and pathogenesis. In the present study, we used Illumina microarray to detect the global gene profile altered in KSHV-infected siHa cervical cancer cell-line containing integrated HPV16 genome.
2017-08-13 | GSE90039 | 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: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:Pre-exposure chemoprophylaxis using antiretroviral agents is a promising strategy for the prevention of sexual HIV transmission in women. Molecular transporters in the human vaginal tract may play a pivotal role in determining drug disposition and, consequently, pharmacodynamic outcomes in these efforts. Little is known, however, on the expression of these transporters in vaginal tissues, representing a critical knowledge gap. Our study analyzed the genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women undergoing gynecologic surgeries. The genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women (20-56 years old) undergoing gynecologic surgeries was measured.
2014-01-29 | E-GEOD-49892 | biostudies-arrayexpress
Project description:Pre-exposure chemoprophylaxis using antiretroviral agents is a promising strategy for the prevention of sexual HIV transmission in women. Molecular transporters in the human vaginal tract may play a pivotal role in determining drug disposition and, consequently, pharmacodynamic outcomes in these efforts. Little is known, however, on the expression of these transporters in vaginal tissues, representing a critical knowledge gap. Our study analyzed the genome-wide transcriptome in 44 vaginal tissue samples from 6 reproductive-age women undergoing gynecologic surgeries.
2014-01-29 | GSE49892 | 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:Tissue mononuclear phagocytes (MNP) are specialised in pathogen detection and antigen presentation. They are the first cells of the immune system to encounter HIV and play a key role in transmission as they deliver the virus to CD4 T cells, which are the primary HIV target cell in which the virus undergoes replication. Most studies have investigated the role that epithelial MNPs play in HIV transmission but, as mucosal trauma and inflammation are strongly associated with HIV transmission, it is also important to examine the role that sub-epithelial MNPs play. Sub-epithelial MNPs are present in a diverse array of subsets which differ in their function and the pathogens they detect. Understanding how specific subsets interact with HIV and deliver the virus to CD4 T cells is therefore of key importance to vaccine and microbicide development. In this study we have shown that, after topical application, HIV can penetrate to interact with sub-epithelial resident myeloid cells in anogenital explants and defined the full array of MNP subsets that are present in all the human anogenital and colorectal sub-epithelial tissues that HIV may encounter during sexual transmission. In doing so we have identified two subsets that preferentially take up HIV, become infected and transmit the virus to CD4 T cells; CD14+CD1c+CD11c+ monocyte-derived dendritic cells and langerin-expressing conventional dendritic cells 2 (cDC2).
2021-03-01 | GSE166639 | GEO
Project description:During sexual transmission of HIV-1 from male to female partners, the vagina is the initial site of contact with HIV infected semen. The mechanism of HIV traversing the CD4 negative multi-layered stratified squamous epithelial barrier of the vagina to infect sub-epithelial susceptible immune cells, is hitherto unknown. HIV gp120 binds to several host proteins on vaginal epithelial cells. To gain an insight into the physiologic changes that may occur in vaginal epithelial cells in response to interactions with HIV gp120, and obtain an understanding of the molecular mechanisms by which HIV breaches the vaginal epithelium, a global snap shot of gene expression profiles in the vaginal epithelial cell line Vk2/E6E7, treated with HIV gp120 was determined. The vaginal epithelial cell line Vk2/E6E7 was treated with HIV gp120 (83nM) for 24 hr, and Agilent one colour, microarrays were performed. Agilent one-color experiment,Organism: Human ,Agilent-Custom Whole Genome Human 8x60k designed by Genotypic Technology Pvt. Ltd. (AMADID: 027114), Labeling kit: Agilent Quick-Amp labeling Kit (p/n5190-0442)
2014-03-01 | E-GEOD-44914 | biostudies-arrayexpress
Project description:During sexual transmission of HIV-1 from male to female partners, the vagina is the initial site of contact with HIV infected semen. The mechanism of HIV traversing the CD4 negative multi-layered stratified squamous epithelial barrier of the vagina to infect sub-epithelial susceptible immune cells, is hitherto unknown. HIV gp120 binds to several host proteins on vaginal epithelial cells. To gain an insight into the physiologic changes that may occur in vaginal epithelial cells in response to interactions with HIV gp120, and obtain an understanding of the molecular mechanisms by which HIV breaches the vaginal epithelium, a global snap shot of gene expression profiles in the vaginal epithelial cell line Vk2/E6E7, treated with HIV gp120 was determined. The vaginal epithelial cell line Vk2/E6E7 was treated with HIV gp120 (83nM) for 24 hr, and Agilent one colour, microarrays were performed.
2014-03-01 | GSE44914 | GEO
Project description:The continuing spread of HIV/AIDS is predominantly fueled by sexual exposure to HIV-contaminated semen. Seminal plasma (SP), the liquid portion of semen, harbors a variety of factors that may favor HIV transmission by facilitating viral entry into host cells, eliciting the production of pro-inflammatory cytokines, and enhancing the translocation of HIV across the genital epithelium. One important and abundant class of factors in SP is extracellular vesicles (EVs), which in general are important intercellular signal transducers. Although numerous studies have characterized blood plasma-derived EVs from both uninfected and HIV-infected individuals, little is known about the properties of EVs from semen of HIV-infected individuals. We report here that fractionated SP enriched for EVs from HIV-infected men induce potent transcriptional responses in epithelial and stromal cells that interface with luminal contents of the female reproductive tract. Compared to semen EV fractions from uninfected individuals, those from acutely-infected individuals induced a more pro-inflammatory signature. This was not associated with any observable differences in the surface phenotypes of the vesicles. However, miRNA expression profiling analysis revealed that EV fractions from infected individuals exhibit a broader and more diverse profile. Taken together, our data suggest that SP EVs from HIV-infected individuals exhibit unique miRNA signatures and exert potent pro-inflammatory transcriptional changes in cells of the female reproductive tract, which may facilitate HIV transmission.
2020-06-18 | GSE152714 | GEO