Phenotype and severity of asthma determines bronchial epithelial immune responses to a viral mimic

Abstract

BackgroundAsthma 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 virus is unclear.ObjectivesTo describe the association between different phenotypes and severity of asthma and bronchial epithelial immune responses to viral stimulation.MethodsIn 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) (TLR3 agonist) in vitro. The expression of TLR3-induced pro-inflammatory and anti-viral responses of BECs were analysed using RT-qPCR and multiplex ELISA and compared across asthma phenotypes and severity of disease.ResultsPatients with atopic asthma had increased induction of IL-4, IFN-β, IL-6, TNF-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 TSLP only in severe eosinophilic asthma.ConclusionsThe 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.