RT Journal Article
SR Electronic
T1 Phenotype and severity of asthma determines bronchial epithelial immune responses to a viral mimic
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 2102333
DO 10.1183/13993003.02333-2021
VO 60
IS 1
A1 Celeste Porsbjerg
A1 Juan Jose Nieto-Fontarigo
A1 Samuel Cerps
A1 Sangheeta Ramu
A1 Mandy Menzel
A1 Morten Hvidtfeldt
A1 Alexander Silberbrandt
A1 Laurits Frøssing
A1 Ditte Klein
A1 Asger Sverrild
A1 Lena Uller
YR 2022
UL http://erj.ersjournals.com/content/60/1/2102333.abstract
AB 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