Derrick, Tamsyn; Ramadhani, Athumani M; Macleod, David; Massae, Patrick; Mafuru, Elias; Aiweda, Malisa; Mbuya, Kelvin; Makupa, William; Mtuy, Tara; Bailey, Robin L; +3 more... Mabey, David CW; Holland, Martin J; Burton, Matthew J; (2020) Immunopathogenesis of Progressive Scarring Trachoma: Results of a 4-Year Longitudinal Study in Tanzanian Children. INFECTION AND IMMUNITY, 88 (4). ISSN 0019-9567 DOI: https://doi.org/10.1128/IAI.00629-19
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Abstract
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 scarring trachoma due to an incomplete understanding of disease pathogenesis. A cohort study was performed in northern Tanzania in 616 children aged 6 to 10 years at enrollment. Every 3 months for 4 years, children were examined for clinical signs of trachoma, and conjunctival swabs were collected for C. trachomatis detection and to analyze the expression of 46 immunofibrogenic genes. Data were analyzed in relation to progressive scarring status between baseline and the final time point. Genes that were significantly associated with scarring progression included those encoding proinflammatory chemokines (CXCL5, CCL20, CXCL13, and CCL18), cytokines (IL23A, IL19, and IL1B), matrix modifiers (MMP12 and SPARCL1), immune regulators (IDO1, SOCS3, and IL10), and a proinflammatory antimicrobial peptide (S100A7). In response to C. trachomatis infection, IL23A and PDGF were significantly upregulated in scarring progressors relative to in nonprogressors. Our findings highlight the importance of innate proinflammatory signals from the epithelium and implicate interleukin 23A (IL-23A)-responsive cells in driving trachomatous scarring, with potential key mechanistic roles for PDGFB, MMP12, and SPARCL1 in orchestrating fibrosis.
Item Type | Article |
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Faculty and Department |
Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology Faculty of Infectious and Tropical Diseases > Dept of Clinical Research |
Research Centre |
Centre for Maternal, Reproductive and Child Health (MARCH) International Centre for Eye Health |
PubMed ID | 31964744 |
Elements ID | 144073 |
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Filename: Immunopathogenesis of Progressive Scarring Trachoma Results of a 4-Year Longitudinal Study in Tanzanian Children.pdf
Licence: Creative Commons: Attribution 3.0
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