PT - JOURNAL ARTICLE AU - Jasmin Krug AU - Alexander Kiefer AU - Julia Koelle AU - Tytti Vuorinen AU - Paraskevi Xepapadaki AU - Barbara Stanic AU - Mircea Chiriac AU - Mübeccel Akdis AU - Theodor Zimmermann AU - Nikolaos G. Papadopoulos AU - Susetta Finotto TI - TLR 7/8 regulates Type I and Type III Interferon Signalling in RV1b induced Allergic Asthma AID - 10.1183/13993003.01562-2020 DP - 2020 Jan 01 TA - European Respiratory Journal PG - 2001562 4099 - http://erj.ersjournals.com/content/early/2020/11/11/13993003.01562-2020.short 4100 - http://erj.ersjournals.com/content/early/2020/11/11/13993003.01562-2020.full AB - Question Interferon responses have been reported to be defective in rhinovirus (RV) induced asthma. The heterodimeric receptor of type I Interferon (IFN) (IFN-α/-β) is composed by IFNαR-1 and IFNαR-2. Ligand binding to the IFN-α/-β receptor complex activates STAT1 and STAT2 intracellularly. Although type III Interferon (IFN-λ) binds to a different receptor containing IFNλRA and IL-10R2, its triggering leads to activation of the same downstream transcription factors. Here we analysed the effects of Rhinovirus to Interferon type I and III receptors and asked about possible Toll-like receptor 7/8 agonist R848 mediated IFNαR1 and IFNλRα regulation.Methods We measured IFN-α, -β, -λ and their receptor levels in PBMCs supernatants and cell pellets stimulated with RV1b and the Toll-like Receptor 7/8 (TLR7/8) agonist (R848), in two cohorts of children with and without asthma recruited at preschool 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 IFNλR mRNA expression in PBMCs of healthy and asthmatic children, but suppressed the IFNαR mRNA levels. In murine lung cells, RV1balone and together with R848 suppressed IFNαR protein in T cells compared to controls and in total lung IFNλR mRNA compared to RV1b infection alone.Answer In PBMCs from pre-school children, IFNαR mRNA was reduced and IFNλRα mRNA was induced upon treatment with TLR7/8 agonist thus suggesting new avenues for induction of anti-viral immune responses in pediatric asthma.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Blanchard has nothing to disclose.Conflict of interest: Jasmin Krug has no conflict of interest to declareDr. Krug reports grants from European Grant PreDicta, grants from DFG grant (CRC1181/TP 08), grants from SFB grant in the CRC 1181, during the conduct of the study;.Conflict of interest: Dr Kiefer A. has no conflict of interestDr. Krug reports grants from European Grant PreDicta, grants from DFG grant (CRC1181/TP 08), grants from SFB grant in the CRC 1181, during the conduct of the study;.Conflict of interest: Koelle J.. has no conflict of interestDr. Krug reports grants from European Grant PreDicta, grants from DFG grant (CRC1181/TP 08), grants from SFB grant in the CRC 1181, during the conduct of the study;.Conflict of interest: Dr. Tytti Vuorinen has nothing to disclose.Dr. Krug reports grants from European Grant PreDicta, grants from DFG grant (CRC1181/TP 08), grants from SFB grant in the CRC 1181, during the conduct of the study;.Dr. Tytti has nothing to disclose.Conflict of interest: Dr. Xepapadaki reports personal fees from Uriach, personal fees from Novartis, personal fees from Nestle, personal fees from Nutricia, outside the submitted work;.Conflict of interest: Dr. Barbara Stanic has nothing to disclose.Dr. Krug reports grants from European Grant PreDicta, grants from DFG grant (CRC1181/TP 08), grants from SFB grant in the CRC 1181, during the conduct of the study;.Dr. Tytti has nothing to disclose.Conflict of interest: Dr. Chiriac reports grants from DFG grant CH1428/2-1, during the conduct of the study;.Dr. Krug reports grants from European Grant PreDicta, grants from DFG grant (CRC1181/TP 08), grants from SFB grant in the CRC 1181, during the conduct of the study;.Conflict of interest: Dr Akdis has no conflict of interestDr. Krug reports grants from European Grant PreDicta, grants from DFG grant (CRC1181/TP 08), grants from SFB grant in the CRC 1181, during the conduct of the study;.Conflict of interest: Dr. Theodor Zimmermann has nothing to disclose.Dr. Krug reports grants from European Grant PreDicta, grants from DFG grant (CRC1181/TP 08), grants from SFB grant in the CRC 1181, during the conduct of the study;.Dr. Tytti has nothing to disclose.Conflict of interest: Dr. Papadopoulos reports personal fees from Novartis, personal fees from Nutricia, personal fees from HAL, personal fees from MENARINI/FAES FARMA, personal fees from SANOFI, personal fees from MYLAN/MEDA, personal fees from BIOMAY, personal fees from AstraZeneca, personal fees from GSK, personal fees from MSD, personal fees from ASIT BIOTECH, personal fees from Boehringer Ingelheim, grants from Gerolymatos International SA, grants from Capricare, outside the submitted work;.Conflict of interest: Prof Susetta Finotto has nothing to disclose.Dr. Krug reports grants from European Grant PreDicta, grants from DFG grant (CRC1181/TP 08), grants from SFB grant in the CRC 1181, during the conduct of the study;.Dr. Tytti has nothing to disclose.