Abstract
Purpose: :
Trachoma, the leading infectious cause of blindness worldwide, is a cicatrising conjunctivitis driven by Chlamydia trachomatis. The immuno-fibrogenic responses involved are poorly understood, which is limiting efforts to develop a vaccine. The purpose of this study was to investigate the major features of the immune response in scarring trachoma by gene expression analysis.
Methods: :
In this study from Ethiopia, individuals with trachomatous trichiasis (TT) were compared to normal controls (NC). Conjunctival swab samples were collected for RNA isolation. Total RNA was extracted. Transcriptone-wide analysis was performed by microarray (WG-6, Illumina) on a limited sub-set of cases and controls. The relative expression levels of various genes of interest indentified by microarray were measured by Real-time RT-PCR.
Results: :
772 people were recruited (386 TT, 386 NC). Microarray experiments were performed on 14NC and 28TT. 4423 genes were regulated at the adj. p<0.001 level. Pathway analysis (GeneGo) found activation of proteolytic pathways and inflammatory cascades. There was extensive evidence of transformation to a keratinised epithelium. Real-time PCR was performed for 16 genes on the full 772 CC set. TT cases had upregulation of Psoriasin (S100A7), IL-1b, IL-19, NOS2A, MMP7, MMP9, MMP12, HAS3, INDO and CXCL5.There was no difference in the expression of INFg while IL-13 was lower in TT.
Conclusions: :
Trachomatous trichiasis was associated with a pro-inflammatory response (S100A7, IL-1b, CXCL5) in the conjunctiva and evidence of altered connective tissue regulation (MMP7, MMP9, MMP12, HAS3). There was evidence of a predominantly TH1 response (INDO raised, IL-13 lower, IL-13RA raised) and classical macrophage activation (NOS2A).
Keywords: trachoma • cytokines/chemokines • conjunctiva