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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PROVIDER: PRJNA693314 | ENA |
REPOSITORIES: ENA
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Project description:Immunological correlates of natural resistance to HIV have been identified in HIV-exposed seronegative (HESN) individuals. The cervicovaginal epithelium has not been studied for such correlates despite constituting an important barrier against sexual HIV transmission. To fill this gap in knowledge, we collected samples of blood and genital mucosa from Kenyan HESN sex workers (n=29) and controls (n=33). The samples were analyzed by several methods including tissue-based RNA sequencing. A significantly higher relative proportion of regulatory T cells and lower proportion of activated cervical T cells were found in the HESN group compared with the controls. However, they had comparable tissue RNA transcriptional profiles. In conclusion, the identification of an increased proportion of regulatory T cells in blood, a lower proportion of activated cervical T cells, and an intact ectocervical microenvironment in HESN individuals add new data to current knowledge about natural resistance to sexual transmission of HIV.
2021-04-20 | GSE165132 | GEO
Project description:Introduction: Structural integrity of the cervical epithelial barrier is crucial for defending the female reproductive tract against sexually transmitted infections, including HIV. Female sex hormones, estradiol and progesterone, play an important role in modulating this epithelial barrier. However, the influence of fluctuating estradiol and progesterone on ectocervical tissue gene and protein expression in naturally cycling women at high risk for sexually transmitted infections is not well understood. Methods: Ectocervical biopsies, cervicovaginal lavage fluid, and venous blood samples were collected from naturally cycling Kenyan female sex workers at two time points, separated by 2 weeks. The first time point represented the luteal phase of the menstrual cycle and the second time point represented the follicular phase. Plasma estradiol and progesterone levels were measured at each time point. Ectocervical tissues were analyzed by RNA-sequencing and in situ immunofluorescence staining. Cervicovaginal lavage samples were evaluated using antibody-based protein profiling. Results: Employing a systems biology approach, we demonstrated that high plasma estradiol levels enhanced ectocervical epithelial integrity. These findings were more pronounced in samples from the follicular phase (when progesterone and estradiol levels were significantly lower) and included increased expression, and more intact distribution, of the desmosomal cadherin DSG1. The effects of progesterone on gene and protein levels, as well as on intact tissue (as visualized by in situ staining), were modest throughout the menstrual cycle. Both estradiol and progesterone levels had limited influence on mucosal immune factors. Conclusion: Estradiol levels were associated with modulation of cervical epithelial barrier integrity, including the expression and distribution of DSG1, during the follicular phase of natural menstrual cycles in Kenyan sex workers.
2025-01-17 | GSE273823 | GEO
Project description:Highly Exposed-Seronegatives (HESN) individuals do not contract HIV-1 infection despite long-term exposure; few comprehensive studies examining behavior, mucosal tissue, and peripheral immune parameters in sexually-exposed HESN have been completed. To this end, we assessed rate of condomless vaginal sex, the immune activation status (peripheral blood) and gene expression (ectocervical biopsies) in female cohort of high-risk female sex workers [FSW] (n=50) and non-sex worker women [CG] (n=32) in San Juan, Puerto Rico, USA. Of the 50 FSWs examined only 5 had detectable anti-HIV responses by either HIV gag-specific CD8+ T-Cell responses or mucosal anti-HIV envelope IgG/IgA. FSW had a uniform lower CD38 expression on circulating CD4+ or CD8+ T-Cells (both: p<0.0001:Wilcoxon Rank Sum). Cervical tissue from FSWs had greater levels of CD4+ T-Cell (p=0.040), CD123+ plasmacytoid Dendritic Cells (p=0.013) and CD68+ macrophage infiltrates (p=0.038). Cervical gene expression by RNA microarray indicated that FSW had a gene signature characterized by lower expression of genes associated with leukocyte homing and chemotaxis; partial interferon regulated gene signature; and lower gene expression of genes required for HIV infection such as CD4 and NUP153 indicating a lower mucosal immune activation state and reduced susceptibility to HIV-1 infection within mucosal tissue. Notably, Interferon (IFN)-ε expression was higher in FSW than CG women, as detected by RNA (microarray) and protein (IHC) expression in cervical epithelium. The observed levels of IFNε were associated with the reported frequency of unprotected intercourse. Finally, IFNε was induced by treatment of the ECT1 cell line with seminal fluid, suggesting that semen exposure may contribute to long-term protection. Decreased levels of immune activation and gene expression required for HIV infection along with semen-induced epithelial Interferon ε production within the reproductive tract of FSWs highlight distinct host intrinsic resistance mechanisms that may contribute to long-term HIV seronegative status in spite of high-risk condomless sex.
2019-11-21 | GSE63441 | GEO
Project description:Drone honey bees are the obligate sexual partners of queens, and the availability of healthy, high-quality drones directly affects the queen's fertility and the productivity of her subsequent colony. Yet, our understanding of how stressors affect drone fertility and physiology is presently limited. Like other male Hymenopterans, drones are haploid and are thus expected to be more sensitive to stressors than workers, as suggested by the haploid susceptibility hypothesis. We used quantitative proteomics to investigate protein expression profiles in the hemolymph of topically exposed workers and drones, and we show that drones express surprisingly high levels of putative stress response proteins - even in the negative control groups - relative to workers. These findings suggest that drones may invest in strong constitutive expression of damage-mitigating proteins for a wide range of stressors, potentially to the detriment of launching a more specific response to new stressors. Regardless of the underlying mechanism, the robust expression patterns of proteins involved in stress responses in drones suggests that drone stress tolerance systems are fundamentally rewired relative to workers, and their susceptibility to stress depends on more than simply gene dose or deleterious recessive alleles.
2021-07-14 | MSV000087818 | MassIVE
Project description:Benzene, a natural component of petroleum products, is a known hematotoxic and leukemogenic agent. The haematotoxic effect and excess leukemia has been reported below 1 ppm, an exposure level previously considered not to cause any health effects. Gene expression studies suggest that benzene affects genes involved in AML and immune response pathways in a supra-linear manner, and at exposure levels as low as 0.1 ppm benzene. An increased risk of haematopoietic malignancies and altered gene expression also at exposure below 1 ppm is compatible with the emerging knowledge of a non-linear metabolism of benzene, favouring production of a greater proportion of toxic metabolites in subjects exposed to benzene concentrations below 1 ppm than in heavily exposed workers. In the present study, we investigated whether workers found to have a dose-dependent decline in relevant immune cells after benzene-exposure deviated from the unexposed referents in global gene expression changes in whole blood samples, and whether any pathways or genes previously reported in similar low-dose gene expression studies were differentially affected. The study population comprised eight benzene-exposed petroleum workers and five referents deemed unexposed to benzene recruited from the catering section on the same offshore installation (for sampling strategy, see sampling protocol). The two groups significantly differed in age. The dataset was therefore balanced for age by excluding workers at age <35 and >55 in the data modelling to identify significant genes.
2017-10-19 | E-MTAB-5331 | biostudies-arrayexpress
Project description:Apis mellifera workers in temperate climates display two castes; short lived summer bees that engage in nursing, hive maintenance and foraging, and long lived winter bees (diutinus bees) which remain within the hive and are essential for thermoregulation. Label free quantitative proteomic analysis was conducted on A. mellifera workers sampled from July to October 2019 to compare the proteomes of workers as the colony progresses through the year. Proteomic analysis revealed a shift in protein expression in workers in September and October in comparison to July and August samples. Workers samples in September and October had a higher abundance of proteins associated with oxidative phosphorylation and storage proteins such as hexamerin. Interestingly, a shift in protein expression was detected in newly emerged bees between July to October, providing evidence that workers have adapted to emerge with a different protein profile in preparation for the winter months.
2022-11-21 | PXD032755 | Pride
Project description:We identified and validated characteristic miRNA expression profiles of human whole blood in workers exposed to volatile organic compounds (VOCs) and compared the usefulness of miRNA indicator of VOCs with the effectiveness of the already used urinary biomarkers of occupational exposure. Using a microarray based approach, we screened and detected deregulated miRNAs in their expression in workers exposed to VOCs (toluene [TOL], xylene [XYL] and ethylbenzene [EBZ]). Total 169 workers from four dockyards were enrolled in current study, and 50 subjects of them were used for miRNA microarray analysis.
2015-03-28 | E-GEOD-67341 | biostudies-arrayexpress
Project description:We identified and validated characteristic miRNA expression profiles of human whole blood in workers exposed to volatile organic compounds (VOCs) and compared the usefulness of miRNA indicator of VOCs with the effectiveness of the already used urinary biomarkers of occupational exposure.
2015-03-28 | GSE67341 | GEO
Project description:The effect of benzene exposure on peripheral blood mononuclear cell (PBMC) gene expression was examined in a population of shoe-factory workers with well-characterized occupational exposures to benzene. We compared data from two microarray platforms (Illumina and Affymetrix). Keywords: occupational exposure
2009-05-11 | GSE9569 | GEO
Project description:Immunological correlates of natural resistance to HIV have been identified in HIV-exposed seronegative (HESN) individuals and include a low-inflammatory genital mucosal status. The cervicovaginal epithelium has not been studied for such correlates despite constituting an important barrier against sexual HIV transmission. To fill this gap in knowledge, we collected samples of blood, cervical mononuclear cells, cervicovaginal lavage, and ectocervical tissue from Kenyan HESN sex workers (n = 29) and controls (n = 33). The samples were analyzed by flow cytometry, protein profiling, 16S rRNA gene sequencing, in situ image analysis, and tissue-based RNA sequencing. A significantly higher relative proportion of regulatory T cells in blood (B7+CD25hiFoxP3+CD127loCD4+ and B7+Helios+FoxP3+CD4+), and a significantly lower proportion of activated cervical T cells (CCR5+CD69+CD4+ and CCR5+CD69+CD8+), were found in the HESN group compared with the controls. In contrast, there were no statistically significant differences between the study groups in cervicovaginal protein and microbiome compositions, ectocervical epithelial thickness, E-cadherin expression, HIV receptor expression, and tissue RNA transcriptional profiles. The identification of an intact ectocervical microenvironment in HESN individuals add new data to current knowledge about natural resistance to sexual transmission of HIV.
| S-EPMC7998094 | biostudies-literature