Deprived TLR9 expression in apparently healthy nasal mucosa might trigger polyp-growth in chronic rhinosinusitis patients

• Published in: PloS one 2014-08, Vol.9 (8), p.e105618-e105618
• Main Authors: Tengroth, Lotta, Arebro, Julia, Kumlien Georén, Susanna, Winqvist, Ola, Cardell, Lars-Olaf
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age; Aged; Aged, 80 and over; Bacterial infections; Biology and Life Sciences; Biopsy; Bone; Cell growth; Chronic Disease; Cytokines; Cytokines - analysis; Cytokines - immunology; Cytometry; Deoxyribonucleic acid; Disease; DNA; Endoscopy; Epithelial cells; Female; Females; Flow cytometry; Granulocyte colony-stimulating factor; Health aspects; Health care; Humans; Immune system; Immunology; Infection; Infections; Interleukin 6; Male; Medicin och hälsovetenskap; Medicine and Health Sciences; Microorganisms; Middle Aged; Mucosa; Nasal Mucosa - immunology; Nasal Mucosa - pathology; Nasal Polyps - immunology; Nasal Polyps - pathology; Nose; Otolaryngology; Patients; Polyps; Proteins; Receptors; Respiratory tract; Rhinitis; Rhinosinusitis; Sinuses; Sinusitis; Sinusitis - immunology; Sinusitis - pathology; Staphylococcus aureus; Stimulation; Surgery; Tissues; TLR9 protein; Toll-Like Receptor 9 - analysis; Toll-Like Receptor 9 - immunology; Toll-like receptors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor Receptor-2 - analysis; Vascular Endothelial Growth Factor Receptor-2 - immunology; Viral diseases; Viral infections; Viruses; Young Adult
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0105618

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. To analyse the role of TLR9 mediated microbial defense in tissue bordering the polyp. 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. 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. 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.