TY - JOUR T1 - Phenotype and severity of asthma determines bronchial epithelial immune responses to a viral mimic JF - European Respiratory Journal JO - Eur Respir J DO - 10.1183/13993003.02333-2021 VL - 60 IS - 1 SP - 2102333 AU - Celeste Porsbjerg AU - Juan Jose Nieto-Fontarigo AU - Samuel Cerps AU - Sangheeta Ramu AU - Mandy Menzel AU - Morten Hvidtfeldt AU - Alexander Silberbrandt AU - Laurits Frøssing AU - Ditte Klein AU - Asger Sverrild AU - Lena Uller Y1 - 2022/07/01 UR - http://erj.ersjournals.com/content/60/1/2102333.abstract N2 - Background Asthma is characterised by an aggravated immune response to respiratory viral infections. This phenomenon is a clinically well-recognised driver of acute exacerbations, but how different phenotypes of asthma respond immunologically to viruses is unclear.Objectives To describe the association between different phenotypes and severity of asthma and bronchial epithelial immune responses to viral stimulation.Methods In the Immunoreact study, healthy subjects (n=10) and 50 patients with asthma were included; 30 (60%) were atopic, and 34 (68%) were eosinophilic; 14 (28%) had severe asthma. All participants underwent bronchoscopy with collection of bronchial brushings. Bronchial epithelial cells (BECs) were expanded and stimulated with the viral replication mimic poly (I:C) (Toll-like receptor (TLR)3 agonist) in vitro. The expression of TLR3-induced pro-inflammatory and antiviral responses of BECs were analysed using reverse transcriptase quantitative PCR and multiplex ELISA and compared across asthma phenotypes and severity of disease.Results Patients with atopic asthma had increased induction of interleukin (IL)-4, interferon (IFN)-β, IL-6, tumour necrosis factor-α, and IL-1β after poly (I:C) stimulation compared to non-atopic patients, whereas in patients with eosinophilic asthma only IL-6 and IL-8 induction was higher than in non-eosinophilic asthma. Patients with severe asthma displayed a decreased antiviral IFN-β, and increased expression of IL-8, most pronounced in atopic and eosinophilic asthmatics. Furthermore, induction of IL-33 in response to poly (I:C) was increased in severe atopic and in severe eosinophilic asthma, but thymic stromal lymphopoietin only in severe eosinophilic asthma.Conclusions The bronchial epithelial immune response to a viral mimic stimulation differs between asthma phenotypes and severities, which may be important to consider when targeting novel asthma treatments.The airway epithelial pro-inflammatory and anti-viral response to a viral stimulus differs with the phenotype and severity of asthma, indicating differences in immune drivers of exacerbations https://bit.ly/3DhTVWw ER -