Sinonasal Epithelial Cell Expression of Toll-Like Receptor 9 is Elevated in Cystic Fibrosis-Associated Chronic Rhinosinusitis

Abstract

Cystic fibrosis (CF) patients frequently suffer from chronic rhinosinusitis (CRS). The extent to which alterations in sinonasal innate immunity contribute to this disease process is unknown. Activation of sinonasal epithelial cell (SNEC) Toll-like receptors (TLRs), an important component of the innate immune system, may be associated with the hyperinflammatory state observed in sinonasal mucosa of CF patients with CRS. This study compares expression of Toll-like receptor 9 (TLR9), in SNRCs collected from CF subjects with CRS to that of normal control subjects. This was a prospective study measuring TLR9 on SNECs collected via endoscopic-guided middle meatal brushings from 8 adult controls and 14 adult subjects with CF-associated CRS. TLR9 expression was significantly elevated in CF subjects at 91% ± 6% when compared with 76% ± 10% in normal controls (p = 0.001). The significantly greater expression of sinonasal epithelial TLR9 in CF likely reflects increased antimicrobial innate immune activity in chronically colonized and frequently infected CF individuals. However, this finding contrasts with previously reported decreased epithelial TLR9 expression in eosinophilic CRS with nasal polyposis and may indicate differential modulation of innate immunity in Th1-predominent CF versus Th2-dominated CRS with nasal polyps, despite both being diseases of sinonasal mucosal inflammation.