title: Active trachoma is associated with increased conjunctival expression of IL17A and profibrotic cytokines.
abstract: The immunological basis of scarring trachoma is not well understood. It is unclear whether it is driven primarily through cell-mediated adaptive or epithelial-cell-derived innate responses. The purpose of this study was to investigate the expression of the inflammatory and fibrogenic mediators which may be involved. We conducted a cross-sectional survey of children living in an untreated trachoma-endemic community in Tanzania. The children were examined for signs of trachoma, and swabs were collected for bacteriological culture and RNA and DNA isolation. Chlamydia trachomatis was detected by the Amplicor PCR test. The expression of the following genes was measured by quantitative reverse transcription-PCR (RT-PCR): S100A7, IL1B, IL17A, IL23A, CXCL5, CCL18, TLR2, NLRP3, KLRD1, CTGF, and MMP9. Four hundred seventy children under the age of 10 years were included. Follicular trachoma (TF) was detected in 65 children (14%), C. trachomatis was detected in 25 (5%), and bacterial pathogens were cultured in 161 (34%). TF was associated with significantly increased expression of S100A7, IL17A, CCL18, CXCL5, and CTGF. Expression was increased further in the presence of papillary inflammation. Nonchlamydial bacterial infection was associated with increased expression of IL17A, CXCL5, CCL18, and KLRD1. IL17A expression was associated with increased expression of S100A7, CXCL5, CCL18, KLRD1, and CTGF. These data are consistent with a role for IL-17A in orchestrating the proinflammatory response in trachoma. Its activity may be promoted either as part of the cell-mediated response or through innate pathways. It may drive a range of proinflammatory factors leading to excessive tissue damage and repair involving fibrosis.
authors.affiliation: London School of Hygiene and Tropical Medicine, London, United Kingdom. matthew.burton@lshtm.ac.uk
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Burton
authors.forename: Athumani
authors.initials: A
authors.lastname: Ramadhani
authors.forename: Helen A
authors.initials: HA
authors.lastname: Weiss
authors.forename: Victor
authors.initials: V
authors.lastname: Hu
authors.forename: Patrick
authors.initials: P
authors.lastname: Massae
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Burr
authors.forename: Wahida
authors.initials: W
authors.lastname: Shangali
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Holland
authors.forename: David C W
authors.initials: DC
authors.lastname: Mabey
authors.forename: Robin L
authors.initials: RL
authors.lastname: Bailey
mesh_terms: D002648:Child; D002675:Child, Preschool; D003228:Conjunctiva / Q000378:metabolism* / Q000473:pathology; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D020381:Interleukin-17 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D013636:Tanzania / Q000453:epidemiology; D014141:Trachoma / Q000453:epidemiology / Q000276:immunology / Q000378:metabolism*
chemical_list: D016207:Cytokines; C508717:IL17A protein, human; D020381:Interleukin-17