Conjunctival transcriptome profiling of Solomon Islanders with active trachoma but without ocular Chlamydia trachomatis infection.
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PROVIDER: PRJNA418586 | ENA |
REPOSITORIES: ENA
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Project description:Trachoma, a preventable blinding eye disease, is initiated by ocular infection with Chlamydia trachomatis (Ct). MicroRNA (miR) are post-transcriptional regulators of gene expression and play a major role in health and disease. We have investigated the miR profile during C. trachomatis infection of epithelial cells in vitro and in vivo during follicular trachoma with current C. trachomatis infection. Small RNA sequencing was carried out on human epithelial cells infected in vitro and on samples from five children with follicular trachoma with current Ct infection and five children with no evidence of clinical trachoma or infection. In vitro two strains of ocular Ct that differ in virulence, A2497 and isogenic plasmid-free A2497 were used to infect epithelial cell lines. RNAseq results were confirmed by qPCR in six in vitro biological replicates and in 163 clinical samples. Differential miR expression was not detected in isolated epithelial cells infected in vitro at 48 hours post infection. HCjE cells, a conjunctival epithelial cell line, have markedly different miR background expression compared to Hep2 cells. The differing miR profiles of Hep2c and HCjE suggest caution should be used when extrapolating data from Hep2 cells to a tissue-specific clinical scenario. In follicular trachoma, miR-155, miR-150, miR-142, miR-181b, miR-181a, miR-342 and miR-132 were up-regulated during current Ct infection. MiR-4728 and miR-184 were down-regulated in follicular trachoma independent of Ct infection. In follicular trachoma, miR expression reflects development and regulation of the immune response during current Ct infection and a prolonged period of wound healing following Ct clearance.
2016-02-04 | GSE69837 | GEO
Project description:The prevalence of trachomatous inflammation–follicular (TF) in Solomon Island children aged 1–9 years is high enough to warrant, among other interventions, mass distribution of azithromycin. However, over 90% of those with TF did not have concurrent Chlamydia trachomatis infection. We analysed the transcriptome of children with TF and Ct infection, children diagnosed with TF but no Ct infection and children with neither TF nor Ct infection to better understand host responses during an episode of TF, and investigate whether it can provide any clues about the aetiology of TF in this context.
2018-02-28 | GSE106961 | GEO
Project description:Results from 29 samples tested on the Affymetrix HG-focused target array identified transcriptional changes characteristic of ocular disease and ocular Chlamydia trachomatis infection phenotypes. Large numbers of differentially regulated genes were demonstrated. These were characteristic of the host defence response and typical of innate responses at epithelial surfaces and infiltrating leukocytes. These results provide an insight into the complexity of the acute response in trachoma. Samples from 29 participants were tested on the HG-Focus target arrays (17 participants with clinical signs of active trachoma and 12 study participants with normal conjunctivas from the same trachoma endemic population as controls). Conjunctival samples from an additional 60 participants were tested on U133 plus 2.0 arrays and are reported elsewhere. This second set of independent samples was used to assess different gene classifier selection methods and validation tests using >8500 common probe-sets shared between HG-focus target and U133 plus 2.0 arrays. Potential biomarkers of disease and infection are identified.
2010-09-03 | E-GEOD-20430 | biostudies-arrayexpress
Project description:Trachoma is a poorly understood immuno-fibrogenic disease process, initiated by Chlamydia trachomatis (Ct). Differences in conjunctival gene expression profiles between Tanzanians with trachomatous conjunctival scarring (with (TSI) and without (TS) inflammation) and controls (C) were investigated to identify relevant host responses. Tarsal conjunctival swab samples were collected for RNA isolation and Ct PCR. Transcriptome-wide microarray experiments were conducted on 41 samples (TSI 13, TS 15, C14). Cases had enrichment in proinflammatory cytokines and chemokines (IL1B, IL8, CXCL5, CCL20); Matrix metalloprotienases (MMP7, MMP9, MMP12); components of the cornified envelope / squamous metaplasia (SPRR2a, SPRR2F).
2011-08-01 | GSE24383 | GEO
Project description:Trachoma is a poorly understood immuno-fibrogenic disease process, initiated by Chlamydia trachomatis (Ct). Differences in conjunctival gene expression profiles between Tanzanians with trachomatous conjunctival scarring (with (TSI) and without (TS) inflammation) and controls (C) were investigated to identify relevant host responses. Tarsal conjunctival swab samples were collected for RNA isolation and Ct PCR. Transcriptome-wide microarray experiments were conducted on 41 samples (TSI 13, TS 15, C14). Cases had enrichment in proinflammatory cytokines and chemokines (IL1B, IL8, CXCL5, CCL20); Matrix metalloprotienases (MMP7, MMP9, MMP12); components of the cornified envelope / squamous metaplasia (SPRR2a, SPRR2F). Case - control study. Conjunctival swab samples were collected from people with trachomatious conjunctival scarring with (TSI) and without (TS) clinically visable inflammation compared to normal controls (C). Total RNA extracted and analysed on the Illumina WG-6 platrom. Additional extensive qRT-PCR work done on a large set of case-control pairs.
2011-07-31 | E-GEOD-24383 | biostudies-arrayexpress
Project description:Conjunctival samples from 60 individuals with and without the clinical signs of active trachoma were analysed on the U133 Plus 2.0 arrays. Global transcriptional changes characteristic of disease and infection phenotypes were identified. Two analysis methods found large numbers of differentially regulated genes and the existence of networks of co-expressed genes. There were signatures characteristic of the host defence response with evidence supporting infiltration of various types of leukocytes and activation of innate responses of epithelial cells. Two separate methods could classify disease and infection phenotype based on transcription signatures with 70% accuracy. These results provide an insight into the complexity of the acute response in trachoma but are able to partly explain the biology of trachoma through the identification of pathways and gene expression sets useful to future studies on chlamydial immunopathogenesis. Conjunctival samples from 60 participants were tested on U133 plus 2.0 arrays (40 participants with clinical signs of active trachoma and 20 controls with normal conjunctivas as before). Samples were further sub-divided based on the detection and quantification of ocular Chlamydia trachomatis load by PCR tests. Gene expression was then assessed using differential expression and construction of co-expression networks. The content of the constructed gene lists which were identified as part of a network or differentially expressed were then tested for enrichment using publically available analysis tools to identify biological pathways expressed in the conjunctiva during C. trachomatis infection and disease episodes.
2010-09-03 | E-GEOD-20436 | biostudies-arrayexpress
Project description:Results from 29 samples tested on the Affymetrix HG-focused target array identified transcriptional changes characteristic of ocular disease and ocular Chlamydia trachomatis infection phenotypes. Large numbers of differentially regulated genes were demonstrated. These were characteristic of the host defence response and typical of innate responses at epithelial surfaces and infiltrating leukocytes. These results provide an insight into the complexity of the acute response in trachoma.
2010-09-03 | GSE20430 | GEO
Project description:Chlamydia trachomatis serovariants are responsible for either Trachoma, the leading cause of infectious blindness or sexually transmitted disease, wherein the endocervix is the most frequently infected site in women. Disease caused by Chlamydia typically involves chronic inflammation and scarring. Recent work with a live-attenuated A2497 plasmid deficient vaccine strain (A2497-) demonstrated protection in nonhuman primates against trachoma and a lack of measurable ocular pathology in A2497- infected monkeys. We therefore performed host cell transcriptome analysis of Hela cells infected with A2497 plasmid-containing (A2497) and A2497- Chlamydia over time. Our results indicate that relative to wild type A2497, the A2497- variant illicits a transcriptome response indicative of lowered inflammation response a delayed apoptosis response, a reduction in immune cell recruitement cytokine expression and a reduction in genes involved in cell proliferation and or fibrosis-like activities. The data provided here suggests a model that may explain how plasmid deficient chlamydia may provide an immuno-protective response without the pathology normally seen with plasmid-containing bacteria. Ct infection with and without plasmid time series
2014-11-25 | E-GEOD-56168 | biostudies-arrayexpress
Project description:Chlamydia trachomatis serovariants are responsible for either Trachoma, the leading cause of infectious blindness or sexually transmitted disease, wherein the endocervix is the most frequently infected site in women. Disease caused by Chlamydia typically involves chronic inflammation and scarring. Recent work with a live-attenuated A2497 plasmid deficient vaccine strain (A2497-) demonstrated protection in nonhuman primates against trachoma and a lack of measurable ocular pathology in A2497- infected monkeys. We therefore performed host cell transcriptome analysis of Hela cells infected with A2497 plasmid-containing (A2497) and A2497- Chlamydia over time. Our results indicate that relative to wild type A2497, the A2497- variant illicits a transcriptome response indicative of lowered inflammation response a delayed apoptosis response, a reduction in immune cell recruitement cytokine expression and a reduction in genes involved in cell proliferation and or fibrosis-like activities. The data provided here suggests a model that may explain how plasmid deficient chlamydia may provide an immuno-protective response without the pathology normally seen with plasmid-containing bacteria.
2014-11-25 | GSE56168 | GEO
Project description:Ocular infection with Chlamydia trachomatis (trachoma) is the leading cause of blindness that results from infection. Chronic inflammation is believed to drive the scarring process and the progressive blinding disease, however the mechanisms by which this occurs are not completely understood. We hypothesized that Micro RNA (miRNA), as key regulators of genes in inflammatory pathways, are involved in the immunopathogenesis and tissue remodeling observed in trachoma. Conjunctival swabs were collected from a total of 63 individuals resident in trachoma endemic communities in The Gambia, West Africa. MiRNA was extracted from the conjunctival swabs of 23 healthy controls (N), 18 cases with trachomatous scarring (TS) and 22 cases with trachomatous scarring in the presence of clinically significant inflammation (TSI) using Qiagen Allprep DNA/RNA/protein kits. Following reverse transcription and pre-amplification, quantitative RT-PCR was performed using TaqMan Array Human MicroRNA genecards (Av2.0 and Bv3.0) on a 7900HT thermal cycler (Life Technologies, Inc). A total of 754 of the most well characterised unique human miRNA from miRBase (www.mirbase.org/) were screened. Data from each array were uploaded and analysed using the high throughput qPCR package in bioconductor R. Samples with a global miRNA median cycle threshold of 40 were filtered out. A and B cards were analysed separately due to differences in performance of samples on each card. In the A card group 40 samples were normalized and tested: 8 TSI, 16 TS and 16 N. In the B card group 29 samples were normalized and tested: 6 TSI, 13 TS and 10 N. Results were normalized by rank invariant normalization as it reduced the coefficient of variation and increased sample distribution homology more than any other normalization procedure tested. Data in each group were tested for differential expression by Limma. 63 total Samples. In the A card group 40 samples were normalized and tested: 8 TSI, 16 TS and 16 N. In the B card group 29 samples were normalized and tested: 6 TSI, 13 TS and 10 N. Results were normalized by rank invariant normalization as it reduced the coefficient of variation and increased sample distribution homology more than any other normalization procedure tested.
2013-06-11 | E-GEOD-37717 | biostudies-arrayexpress