Journal Article

S119Roles of TLR3, TLR4- and TLRs7-9 in Interferon Induction in Bronchial Epithelial Cells and Peripheral Blood Mononuclear Cells from Asthmatic and Non-Asthmatic Subjects

Rosario, A del, Kon, OM, Sykes, A, Edwards, M R, Macintyre, J, Johnston, S L

2012

Overview

IntroductionDefective rhinovirus (RV) induced interferon (IFN)- beta and IFN- lambda production has been reported in primary human bronchial epithelial cells (HBECs) and peripheral blood mononuclear cells (PBMCs) from asthmatics. The mechanisms of defective IFN induction in asthma are unknown. Virus infection can induce IFNs through Toll like Receptors (TLR)3, TLR4 and TLRs7-9 and TLR agonists have been identified as potential therapeutic options for asthma. The role of these TLRs in IFN induction in asthma is unclear.ObjectiveTo investigate IFN responses to TLR stimulation in HBECs and PBMCs from atopic asthmatic and non-asthmatic individuals.MethodsHBECs and PBMCs from atopic asthmatic and non-asthmatic subjects were stimulated with agonists to TLR3, TLR4 & TLRs7-9 and type I and III IFN responses assessed by qPCR and ELISA.ResultsTLR3 and TLR7, but not TLR4, 8 or 9, stimulation induced IFN protein and mRNA expression in HBECs and PBMCs. IFNs induced were IFN- beta and predominantly type III IFN- lambda in HBECs and type I (- alpha and - beta ) with no IFN- lambda in PBMCs. TLR function was not defective in asthmatic compared to non-asthmatic subjects.ConclusionsTLR3 & TLR7 were the predominant TLRs involved in IFN induction in HBECs and PBMCs. Defective IFN induction to TLR agonists was not observed in these well controlled asthmatic subjects. TLR3/7 agonists could be effective in inducing IFNs in more severe/less well controlled asthmatics who may have deficient virus induced IFN production.

• Subject: Rhinovirus