title: Inverse relationship between microRNA-155 and -184 expression with increasing conjunctival inflammation during ocular Chlamydia trachomatis infection.
abstract: BACKGROUND
  Trachoma, a preventable blinding eye disease, is initiated by ocular infection with Chlamydia trachomatis (Ct). We previously showed that microRNAs (miR) -147b and miR-1285 were up-regulated in inflammatory trachomatous scarring. During the initial stage of disease, follicular trachoma with current Ct infection, the differential expression of miR has not yet been investigated.
  
  
  METHODS
  Conjunctival samples were collected from 163 children aged 1-9 years old living in a trachoma-endemic region of Guinea Bissau, West Africa. Small RNA sequencing (RNAseq) was carried out on samples from five children with follicular trachoma and current Ct infection and five children with healthy conjunctivae and no Ct infection. Small RNAseq was also carried out on human epithelial cell lines infected with ocular Ct strains A2497 and isogenic plasmid-free A2497 in vitro. Results were validated by quantitative PCR (qPCR) in 163 clinical samples.
  
  
  RESULTS
  Differential expression of RNAseq data identified 12 miR with changes in relative expression during follicular trachoma, of which 9 were confirmed as differentially expressed by qPCR (miR-155, miR-150, miR-142, miR-181b, miR-181a, miR-342, miR-132, miR-4728 and miR-184). MiR-155 and miR-184 expression had a direct relationship with the degree of clinical inflammation. MiR-155 was up-regulated (OR = 2.533 ((95 % CI = 1.291-4.971); P = 0.0069) and miR-184 was down-regulated (OR = 0.416 ((95 % CI = 0.300-0.578); P = 1.61*10(-7)) as the severity of clinical inflammation increased. Differential miR expression was not detected in HEp-2 or HCjE epithelial cells 48 h post infection with Ct in vitro. HCjE cells, a conjunctival epithelial cell line, had a markedly different miR background expression compared to HEp-2 cells.
  
  
  CONCLUSIONS
  In follicular trachoma, expression of miR-155 and miR-184 is correlated with the severity of inflammation. This likely reflects host regulation of the immune response and a prolonged period of wound healing following the clearance of Ct. Prolonged healing may be associated with subsequent development of scarring trachoma.
authors: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. tamsyn.derrick@lshtm.ac.uk.
authors: Tamsyn
authors: T
authors: Derrick
authors: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. Anna.Last@lshtm.ac.uk.
authors: Anna R
authors: AR
authors: Last
authors: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. Sarah.Burr@lshtm.ac.uk.|Disease Control and Elimination Theme, Medical Research Council Unit The Gambia, Fajara, The Gambia. Sarah.Burr@lshtm.ac.uk.
authors: Sarah E
authors: SE
authors: Burr
authors: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. Chrissy.Roberts@lshtm.ac.uk.
authors: Chrissy H
authors: CH
authors: Roberts
authors: Programa Nacional de Saúde de Visão, Ministério de Saúde Publica, Bissau, Guinea Bissau. pnlcegueira@yahoo.com.br.
authors: Meno
authors: M
authors: Nabicassa
authors: Programa Nacional de Saúde de Visão, Ministério de Saúde Publica, Bissau, Guinea Bissau. eunicassama27@gmail.com.
authors: Eunice
authors: E
authors: Cassama
authors: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. Robin.Bailey@lshtm.ac.uk.
authors: Robin L
authors: RL
authors: Bailey
authors: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. David.Mabey@lshtm.ac.uk.
authors: David C W
authors: DC
authors: Mabey
authors: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. Matthew.Burton@lshtm.ac.uk.
authors: Matthew J
authors: MJ
authors: Burton
authors: Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom. Martin.holland@lshtm.ac.uk.
authors: Martin J
authors: MJ
authors: Holland
mesh_terms: D001766:Blindness; D002648:Child; D002675:Child, Preschool; D002692:Chlamydia trachomatis / Q000276:immunology*; D003228:Conjunctiva / Q000276:immunology* / Q000469:parasitology; D015536:Down-Regulation; D005260:Female; D005786:Gene Expression Regulation; D006169:Guinea-Bissau; D006801:Humans; D007223:Infant; D007249:Inflammation; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D014141:Trachoma / Q000276:immunology* / Q000469:parasitology; D015854:Up-Regulation
chemical_list: C524942:MIRN155 microRNA, human; C534424:MIRN184 microRNA, human; D035683:MicroRNAs