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Inflammatory cell phenotype and activation in asthma
S119 Roles of TLR3, TLR4- and TLRs7–9 in Interferon Induction in Bronchial Epithelial Cells and Peripheral Blood Mononuclear Cells from Asthmatic and Non-Asthmatic Subjects
  1. A Sykes1,
  2. MR Edwards2,
  3. J Macintyre1,
  4. A del Rosario1,
  5. OM Kon1,
  6. SL Johnston1
  1. 1Imperial College London and Imperial Healthcare NHS Trust, London, UK
  2. 2Imperial College London, London, UK

Abstract

Introduction Defective rhinovirus (RV) induced interferon (IFN)-β and IFN-λ 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.

Objective To investigate IFN responses to TLR stimulation in HBECs and PBMCs from atopic asthmatic and non-asthmatic individuals.

Methods HBECs 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.

Results TLR3 and TLR7, but not TLR4, 8 or 9, stimulation induced IFN protein and mRNA expression in HBECs and PBMCs. IFNs induced were IFN-β and predominantly type III IFN-λ in HBECs and type I (–α and –β) with no IFN-λ in PBMCs. TLR function was not defective in asthmatic compared to non-asthmatic subjects.

Conclusions TLR3 & 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.

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