TY - JOUR
TI - TLR7/8 regulates type I and type III interferon signalling in rhinovirus 1b-induced allergic asthma
AU - Krug, J.
AU - Kiefer, A.
AU - Koelle, J.
AU - Vuorinen, T.
AU - Xepapadaki, P.
AU - Stanic, B.
AU - Chiriac, M.T.
AU - Akdis, M.
AU - Zimmermann, T.
AU - Papadopoulos, N.G.
AU - Finotto, S.
JO - The European respiratory journal
PY - 2021
VL - 57
TODO - 5
SP - null
PB - European Respiratory Society
SN - null
TODO - 10.1183/13993003.01562-2020
TODO - alpha interferon;  alpha interferon receptor;  beta interferon;  beta interferon receptor;  gamma interferon;  gamma interferon receptor;  interleukin 10;  messenger RNA;  resiquimod;  toll like receptor 7;  toll like receptor 8;  interferon;  lambda interferon;  TLR7 protein, human;  toll like receptor 7, age;  allergic asthma;  animal cell;  animal experiment;  animal model;  animal tissue;  Article;  CD4+ T lymphocyte;  CD8+ T lymphocyte;  cell isolation;  cell stimulation;  child;  clinical article;  cohort analysis;  controlled study;  drug mechanism;  female;  human;  human cell;  immune response;  immunostimulation;  immunosuppressive treatment;  interferon production;  longitudinal study;  lung alveolus cell;  male;  mouse;  nonhuman;  pediatric patient;  peripheral blood mononuclear cell;  preschool child;  priority journal;  Rhinovirus;  rhinovirus 1b;  school child;  supernatant;  type I interferon signaling;  type III interferon signaling;  upregulation;  animal;  asthma;  mononuclear cell, Animals;  Asthma;  Child;  Humans;  Interferons;  Leukocytes, Mononuclear;  Mice;  Rhinovirus;  Toll-Like Receptor 7
TODO - Introduction: Interferon (IFN) responses have been reported to be defective in rhinovirus (RV)-induced asthma. The heterodimeric receptor of type I IFN (IFN-α/β) is composed of IFN-αR1 and IFN-αR2. Ligand binding to the IFN-α/β receptor complex activates signal transducer and activator of transcription (STAT) proteins STAT1 and STAT2 intracellularly. Although type III IFN (IFN-λ) binds to a different receptor containing IFN-λR1 and interleukin-10R2, its triggering leads to activation of the same downstream transcription factors. Here, we analysed the effects of RV on IFN type I and III receptors, and asked about possible Toll-like receptor 7/8 (TLR7/8) agonist R848-mediated IFN-αR1 and IFN-λR1 regulation. Methods: We measured IFN-α, IFN-β and IFN-λ and their receptor levels in peripheral blood mononuclear cell (PBMC) supernatants and cell pellets stimulated with RV1b and R848 in two cohorts of children with and without asthma recruited at pre-school age (PreDicta) and at primary school age (AGENDAS) as well as in cell supernatants from total lung cells isolated from mice. Results: We observed that R848 induced IFN-λR mRNA expression in PBMCs of healthy and asthmatic children, but suppressed IFN-αR mRNA levels. In murine lung cells, RV1b alone and together with R848 suppressed IFN-αR protein in T-cells compared with controls and in total lung IFN-λR mRNA compared with RV1b infection alone. Conclusions: In PBMCs from pre-school age children, IFN-αR mRNA was reduced and IFN-λR1 mRNA was induced upon treatment with the TLR7/8 agonist R848, thus suggesting new avenues for induction of antiviral immune responses in paediatric asthma. Copyright © ERS 2021
ER -