Open AccessImmunopathogenesis of Progressive Scarring Trachoma: Results of a 4-Year Longitudinal Study in Tanzanian Children
Author(s) -
Tamsyn Derrick,
Athumani Ramadhani,
David Macleod,
Patrick Massae,
Elias Mafuru,
Aiweda Malisa,
Kelvin Mbuya,
William Makupa,
Tara Mtuy,
Robin L. Bailey,
David Mabey,
Martin J. Holland,
Matthew J. Burton
Publication year - 2020
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.00629-19
Subject(s) - trachoma , chlamydia trachomatis , tanzania , chlamydia , cohort , immunology , azithromycin , medicine , longitudinal study , disease , pediatrics , biology , pathology , antibiotics , microbiology and biotechnology , environmental science , environmental planning
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.