Conjunctival transcriptome profiling of Solomon Islanders with active trachoma but without ocular Chlamydia trachomatis infection.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE106961 | GEO | 2018/02/28
REPOSITORIES: GEO
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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:Trachoma is a poorly understood immuno-fibrogenic disease process, initiated by Chlamydia trachomatis (Ct). Differences in conjunctival gene expression profiles between Ethiopians with trachomatous trichiasis (with (TTI) and without (TT) inflammation) and controls (NC) 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 42 samples (TTI 13, TT 15, NC14). Specific results were confirmed using multiplex quantitative RT-PCR for 16 mRNA targets in an independent collection of case-control samples: 386 case-control pairs (TTI 244, TT 142, NC 386). The gene expression profiles of cases were consistent with: squamous metaplasia (Keratins, SPRR), pro-inflammatory cytokine production (IL-1β, CXCL5, S100A7) and tissue remodelling (MMP7, MMP9, MMP12, HAS3). There was no difference in the level of IFNG between cases and controls. However, cases had increased INDO, NOS2A, and IL13RA2 and reduced IL13. Ct was detected in 1/772. Cases show evidence of ongoing inflammation and tissue remodelling, which were more marked where clinical inflammation was also present. Significantly, these processes appear to be active in the absence of current Ct infection. There was limited evidence of a TH1 response (INDO, NOS2A) and no association between a TH2 response and cases. The epithelium appears actively involved in late cicatricial stages of trachoma through production of pro-inflammatory factors (IL-1β, CXCL5, S100A7). Longitudinal studies are needed to investigate which aetiological factors and pathways are associated with progressive scarring and whether simply controlling chlamydial infection will halt progression in people with established cicatricial disease.
2011-08-01 | GSE23705 | GEO
Project description:Trachoma is a poorly understood immuno-fibrogenic disease process, initiated by Chlamydia trachomatis (Ct). Differences in conjunctival gene expression profiles between Ethiopians with trachomatous trichiasis (with (TTI) and without (TT) inflammation) and controls (NC) 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 42 samples (TTI 13, TT 15, NC14). Specific results were confirmed using multiplex quantitative RT-PCR for 16 mRNA targets in an independent collection of case-control samples: 386 case-control pairs (TTI 244, TT 142, NC 386). The gene expression profiles of cases were consistent with: squamous metaplasia (Keratins, SPRR), pro-inflammatory cytokine production (IL-1β, CXCL5, S100A7) and tissue remodelling (MMP7, MMP9, MMP12, HAS3). There was no difference in the level of IFNG between cases and controls. However, cases had increased INDO, NOS2A, and IL13RA2 and reduced IL13. Ct was detected in 1/772. Cases show evidence of ongoing inflammation and tissue remodelling, which were more marked where clinical inflammation was also present. Significantly, these processes appear to be active in the absence of current Ct infection. There was limited evidence of a TH1 response (INDO, NOS2A) and no association between a TH2 response and cases. The epithelium appears actively involved in late cicatricial stages of trachoma through production of pro-inflammatory factors (IL-1β, CXCL5, S100A7). Longitudinal studies are needed to investigate which aetiological factors and pathways are associated with progressive scarring and whether simply controlling chlamydial infection will halt progression in people with established cicatricial disease. Case - control study. Conjunctival swab samples were collected from people with trachomatous trichiasis with (TTI) and without (TT) 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-23705 | biostudies-arrayexpress
Project description:Sexually transmitted infections (STIs) are commonly reported among HIV-1 infected patients. The increasing prevalence of the most common STI, Chlamydia trachomatis (CT), among HIV-1 infected people suggests a role in HIV-1 infectivity. However, the mechanisms modulating the enhancement of HIV-1 infectivity during HIV-1/STIs coinfection remain elusive. The stimulation of CD4 T cells during CT infection may modulate the expression of specific genes, which in turn enhance the susceptibility and infectivity of CT-specific CD4 T cells to HIV-1 infection. After three days of CT stimulation of PBMCs followed by 3 days of HIV-1 infection, we observed a significant increase in HIV-1 p24 levels among clinically diagnosed C. trachomatis-infected patients as compared to cells from healthy donors. Similarly, ex vivo CT antigen-stimulated PBMCs from healthy donors showed enhanced susceptibility to HIV-1 as compared to unstimulated PBMCs. CT-specific CD4 T cells also harbour more HIV-1 copy numbers as compared to healthy unstimulated CD4 T cells. RNA-seq data revealed the upregulation of CCR chemokine receptors and cytokines in CD4 T cells from CT-stimulated CD4 T cells infected with HIV-1.
2021-12-31 | GSE164264 | GEO
Project description:BACKGROUND:Clinical signs of active (inflammatory) trachoma are found in many children in the Solomon Islands, but the majority of these individuals have no serological evidence of previous infection with Chlamydia trachomatis. In Temotu and Rennell and Bellona provinces, ocular infections with C. trachomatis were seldom detected among children with active trachoma; a similar lack of association was seen between active trachoma and other common bacterial and viral causes of follicular conjunctivitis. Here, we set out to characterise patterns of gene expression at the conjunctivae of children in these provinces with and without clinical signs of trachomatous inflammation-follicular (TF) and C. trachomatis infection. METHODS:Purified RNA from children with and without active trachoma was run on Affymetrix GeneChip Human Transcriptome Array 2.0 microarrays. Profiles were compared between individuals with ocular C. trachomatis infection and TF (group DI; n?=?6), individuals with TF but no C. trachomatis infection (group D; n?=?7), and individuals without TF or C. trachomatis infection (group N; n?=?7). Differential gene expression and gene set enrichment for pathway membership were assessed. RESULTS:Conjunctival gene expression profiles were more similar within-group than between-group. Principal components analysis indicated that the first and second principal components combined explained almost 50% of the variance in the dataset. When comparing the DI group to the N group, genes involved in T-cell proliferation, B-cell signalling and CD8+ T cell signalling pathways were differentially regulated. When comparing the DI group to the D group, CD8+ T-cell regulation, interferon-gamma and IL17 production pathways were enriched. Genes involved in RNA transcription and translation pathways were upregulated when comparing the D group to the N group. CONCLUSIONS:Gene expression profiles in children in the Solomon Islands indicate immune responses consistent with bacterial infection when TF and C. trachomatis infection are concurrent. The transcriptomes of children with TF but without identified infection were not consistent with allergic or viral conjunctivitis.
| S-EPMC5822555 | biostudies-literature
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:BackgroundTrachoma, caused by ocular infection with Chlamydia trachomatis, remains the leading infectious cause of blindness and in 2002 was responsible for 3.6% of total global blindness. Although transmission can be successfully interrupted using antibiotics and improvements in public and personal hygiene, the long-term success of the control programmes advocated by the World Health Organization are still uncertain. For the complete control and prevention of trachoma, a vaccine would be highly desirable. Currently there are no licensed vaccines for trachoma, and no human vaccine trials have been conducted since the 1960s. A barrier to new attempts to design and introduce a vaccine is the identification of immunologic correlates of protective immunity or immunopathology. We studied important correlates of the immune response in a trachoma-endemic population in order to improve our knowledge of this disease. This is essential for the successful development of a vaccine against both ocular and genital C. trachomatis infection.Methods and findingsWe used quantitative real-time PCR for C. trachomatis 16S rRNA to identify conjunctival infection. The expression of IFN-gamma, IDO, IL-10, and FOXP3 mRNA transcripts was measured. We evaluated the role of immune effector and regulatory responses in the control of chlamydial infection and in the resolution of clinical signs of trachoma in endemic communities in Gambia. All host transcripts examined were detectable even in normal conjunctiva. The levels of these transcripts were increased, compared to normal uninfected conjunctiva, when infection was detected, with or without clinical disease signs. Interestingly, when clinical disease signs were present in the absence of infection, the expression of a regulatory T cell transcription factor, FOXP3, remained elevated.ConclusionsThere is evidence of an increase in the magnitude of the local anti-chlamydial cytokine immune responses with age. This increase is coupled to a decline in the prevalence of infection and active trachoma, suggesting that effective adaptive immunity is acquired over a number of years. The anti-chlamydial and inflammatory immune response at the conjunctival surface, which may control chlamydial replication, is closely matched by counter inflammatory or regulatory IL-10 expression. Differences in the level of FOXP3 expression in the conjunctiva may indicate a role for regulatory T cells in the resolution of the conjunctival immune response, which is important in protection from immunopathology. However, the expression of cytokines that control chlamydial replication and those that regulate the conjunctival immune response is not simply juxtaposed; the interaction between the infection and the clinical disease process is therefore more complex.
| S-EPMC1526769 | biostudies-literature
Project description:BackgroundTrachoma is endemic in several Pacific Island states. Recent surveys across the Solomon Islands indicated that whilst trachomatous inflammation-follicular (TF) was present at levels warranting intervention, the prevalence of trachomatous trichiasis (TT) was low. We set out to determine the relationship between chlamydial infection and trachoma in this population.MethodsWe conducted a population-based trachoma prevalence survey of 3674 individuals from two Solomon Islands provinces. Participants were examined for clinical signs of trachoma. Conjunctival swabs were collected from all children aged 1-9 years. We tested swabs for Chlamydia trachomatis (Ct) DNA using droplet digital PCR. Chlamydial DNA from positive swabs was enriched and sequenced for use in phylogenetic analysis.ResultsWe observed a moderate prevalence of TF in children aged 1-9 years (n = 296/1135, 26.1%) but low prevalence of trachomatous inflammation-intense (TI) (n = 2/1135, 0.2%) and current Ct infection (n = 13/1002, 1.3%) in children aged 1-9 years, and TT in those aged 15+ years (n = 2/2061, 0.1%). Ten of 13 (76.9%) cases of infection were in persons with TF or TI (p = 0.0005). Sequence analysis of the Ct-positive samples yielded 5/13 (38%) complete (>95% coverage of reference) genome sequences, and 8/13 complete plasmid sequences. Complete sequences all aligned most closely to ocular serovar reference strains.DiscussionThe low prevalence of TT, TI and Ct infection that we observed are incongruent with the high proportion of children exhibiting signs of TF. TF is present at levels that apparently warrant intervention, but the scarcity of other signs of trachoma indicates the phenotype is mild and may not pose a significant public health threat. Our data suggest that, whilst conjunctival Ct infection appears to be present in the region, it is present at levels that are unlikely to be the dominant driving force for TF in the population. This could be one reason for the low prevalence of TT observed during the study.
| S-EPMC5014345 | biostudies-literature
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:Trachoma, caused by Chlamydia trachomatis (Ct), is the leading infectious blinding disease worldwide. Chronic conjunctival inflammation develops in childhood and leads to eyelid scarring and blindness in adulthood. The immune response to Ct provides only partial protection against re-infection, which can be frequent. Moreover, the immune response is central to the development of scarring pathology, leading to loss of vision. Here we review the current literature on both protective and pathological immune responses in trachoma. The resolution of Ct infection in animal models is IFN?-dependent, involving Th1 cells, but whether this is the case in human ocular infection still needs to be confirmed. An increasing number of studies indicate that innate immune responses arising from the epithelium and other innate immune cells, along with changes in matrix metalloproteinase activity, are important in the development of tissue damage and scarring. Current trachoma control measures, which are centred on repeated mass antibiotic treatment of populations, are logistically challenging and have the potential to drive antimicrobial resistance. A trachoma vaccine would offer significant advantages. However, limited understanding of the mechanisms of both protective immunity and immunopathology to Ct remain barriers to vaccine development.
| S-EPMC3573101 | biostudies-other