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Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE69837 | GEO | 2016/02/04

SECONDARY ACCESSION(S): PRJNA286886

REPOSITORIES: GEO

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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.

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Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection

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