Trachoma is initiated during childhood following repeated conjunctival infection with Chlamydia trachomatis, which causes a chronic inflammatory response in some individuals that leads to scarring and in -turning of the eyelids in later life. There is currently no treatment to halt the progression of 33 scarring trachoma due to an incomplete understanding of disease pathogenesis. A cohort study was performed in northern Tanzania in  children aged 6 -10 at enrolment. Every three months for four years, children were examined for clinical signs of trachoma and conjunctival swabs 37 were collected for C. trachomatis detection and to analyse the expression of 46 immun o -fibrogenic 38 genes. Data were analysed in relation to progressive scarring status between baseline and the final time  point.  Genes that were significantly associated with scarring progression included pro -inflammatory 42 chemokines (CXCL5, CCL20, CXCL13, CCL18), cytokines (IL23A, IL19, IL1B), matrix modifiers (MMP12, 43 SPARCL1), immune -regulators (IDO1, SOCS3, IL10) and pro -inflammatory antimicrobial peptide S100A7. 44 IL23A and PDGF were significantly upregulated in scarring progressors in response to C. trachomatis 45 infection relative to non -progressors.  Our findings highlight the importance of innate pro -inflammatory signals from the epithelium and implicate IL -23A -responsive cells in driving trachomatous scarring, with potential key mechanistic roles 49 for PDGFB, MMP12 and SPARCL1 in orchestrating fibrosis.  

Methods 

Ethical approval This study was reviewed and approved by the Tanzanian National Institute for Medical Research,  Kilimanjaro Christian Medical Centre, and the London School of Hygiene & Tropical Medicine Ethics  Committees and it adhered to the tenets of the Declaration of Helsinki. Written informed consent from 1 a parent or legal guardian was requested from all study participants after detailed explanation in Swahili  or Maa in the presence of a third person. A witnessed thumbprint was acceptable for consent if the individual was unable to read or write.