title: Deprived TLR9 expression in apparently healthy nasal mucosa might trigger polyp-growth in chronic rhinosinusitis patients.
abstract: BACKGROUND
  The origin of nasal polyps in chronic rhinosinusitis is unknown, but the role of viral infections in polyp growth is clinically well established. Toll-like receptors (TLRs) have recently emerged as key players in our local airway defense against microbes. Among these, TLR9 has gained special interest in viral diseases. Many studies on chronic rhinosinusitis with nasal polyps (CRSwNP) compare polyp tissue with nasal mucosa from polyp-free individuals. Knowledge about changes in the turbinate tissue bordering the polyp tissue is limited.
  
  
  OBJECTIVE
  To analyse the role of TLR9 mediated microbial defense in tissue bordering the polyp.
  
  
  METHODS
  Nasal polyps and turbinate tissue from 11 patients with CRSwNP and turbinate tissue from 11 healthy controls in total were used. Five biopsies from either group were analysed immediately with flow cytometry regarding receptor expression and 6 biopsies were used for in vitro stimulation with a TLR9 agonist, CpG. Cytokine release was analysed using Luminex. Eight patients with CRSwNP in total were intranasally challenged with CpG/placebo 24 hours before surgery and the biopsies were collected and analysed as above.
  
  
  RESULTS
  TLR9 expression was detected on turbinate epithelial cells from healthy controls and polyp epithelial cells from patients, whereas TLR9 was absent in turbinate epithelial cells from patients. CpG stimulation increased the percentage cells expressing TLR9 and decreased percentage cells expressing VEGFR2 in turbinate tissue from patients. After CpG stimulation the elevated levels of IL-6, G-CSF and MIP-1β in the turbinate tissue from patients were reduced towards the levels demonstrated in healthy controls.
  
  
  CONCLUSIONS
  Defects in the TLR9 mediated microbial defense in the mucosa adjacent to the anatomic origin of the polyp might explain virus induced polyp growth. CpG stimulation decreased VEGFR2, suggesting a role for CpG in polyp formation. The focus on turbinate tissue in patients with CRSwNP opens new perspectives in CRSwNP-research.
authors.affiliation: Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lotta
authors.initials: L
authors.lastname: Tengroth
authors.affiliation: Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Julia
authors.initials: J
authors.lastname: Arebro
authors.affiliation: Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Susanna
authors.initials: S
authors.lastname: Kumlien Georén
authors.affiliation: Department of Medicine, Unit of Translational Immunology, Karolinska Institute, Stockholm, Sweden.
authors.forename: Ola
authors.initials: O
authors.lastname: Winqvist
authors.affiliation: Division of Ear, Nose and Throat Diseases, Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lars-Olaf
authors.initials: LO
authors.lastname: Cardell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002908:Chronic Disease; D016207:Cytokines / Q000032:analysis / Q000276:immunology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009297:Nasal Mucosa / Q000276:immunology / Q000473:pathology*; D009298:Nasal Polyps / Q000276:immunology / Q000473:pathology*; D012852:Sinusitis / Q000276:immunology / Q000473:pathology*; D051217:Toll-Like Receptor 9 / Q000032:analysis* / Q000276:immunology; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000032:analysis / Q000276:immunology; D055815:Young Adult
chemical_list: D016207:Cytokines; C495371:TLR9 protein, human; D051217:Toll-Like Receptor 9; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2