Reduced TLR2 gene expression is a feature of chronic rhinitic mucosa supporting the hygiene hypothesis

Abstract

Objective. Pathogenic induction of the immunomodulators toll like receptors (TLRs) and beta-defensins (HBD) can steer the developing immune system toward a Th1 nonallergic pathway and might explain why farmer's children show reduced frequency of allergy. We hypothesised that chronic allergic and nonallergic rhinitis might be associated with reduced mucosal levels of TLRs and HBDs. Method. The gene expression levels of TLR2 & 4 and HBD1-4 was determined by real-time polymerase chain reaction in sections of nasal turbinate tissue from adults with persistent allergic and idiopathic rhinitis, healthy nasal mucosa and tonsil tissue. Immunohistochemistry was used to study the localisation and distribution of proteins for TLR2, HBD2, α-defensins (1-3) and neutrophil elastase Results. A significant reduction in TLR2 mRNA expression was identified in allergic mucosa compared to control mucosa, with generally reduced expression for TLR4 and HBDs. While not significant, the nonallergic group also showed reduced expression for TLRs and HBDs. With the exception of HBD4, increased gene levels were seen in tonsil tissue. HBD2 and TLR2 protein expression was localised in lining and submucosal glandular epithelium but insignificant differences were seen for HBDs, TLRs, neutrophils and α-defensin between the rhinitic and control patient groups. Conclusion. Chronic rhinitic mucosa shows reduced levels of TLR and HBD gene expression. The significant reduction in TLR2 gene expression in adult allergics support the concept that increased TLR2 is protective against the development of allergy.