Deprived TLR9 Expression in Apparently Healthy Nasal Mucosa Might Trigger Polyp-Growth in Chronic Rhinosinusitis Patients

Abstract

BackgroundThe 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.ObjectivesTo analyse the role of TLR9 mediated microbial defense in tissue bordering the polyp.MethodsNasal 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.ResultsTLR9 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.ConclusionDefects 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.

Expression of Toll‐like receptors in nasal epithelium in allergic rhinitis

“…Probably partly due to differences in the study set up, they demonstrated a more apical location of TLR3 and an increase in expression of TLRs 2, 3, 4 proteins following the allergen challenge pre-season, but an increase only in TLR3 mRNA during the pollen season (29 in polyp tissue, whereas TLR9 was absent in turbinates from CRSwNP patients. CpG stimulation resulted in an upregulation of TLR9 and modulation of cytokines in turbinate tissue from patients, suggesting that defects in the TLR9 mediated microbial defense in the turbinate might explain virus-induced polyp growth (37). Several studies have observed TLRs in the atopic lower airway inflammation.…”

Molecular Mechanisms of Nasal Epithelium in Rhinitis and Rhinosinusitis

“…Interestingly, epithelial expression of TLR9 was detected in turbinates from healthy controls and in polyp tissue, whereas TLR9 was absent in turbinates from CRSwNP patients. CpG stimulation resulted in an upregulation of TLR9 and modulation of cytokines in turbinate tissue from patients, suggesting that defects in the TLR9-mediated microbial defense in the turbinate might explain virus-induced polyp growth [ 77 ].…”

Role of Toll‐like receptor 9 signaling on activation of nasal polyp–derived fibroblasts and its association with nasal polypogenesis

“…Several studies have reported that whole mucosal tissue and epithelial‐specific TLR9 expression is decreased in CRSwNP. For instance, Tengroth et al . found from CRSwNP patients that TLR9 expression was decreased in turbinate epithelial cells, and Lauriello et al .…”