TY - JOUR

T1 - Phenotype and severity of asthma determines bronchial epithelial immune responses to a viral mimic

AU - Porsbjerg, Celeste

AU - Nieto-fontarigo, Juan Jose

AU - Cerps, Samuel

AU - Ramu, Sangheeta

AU - Menzel, Mandy

AU - Hvidtfeldt, Morten

AU - Silberbrandt, Alexander

AU - Froessing, Laurits

AU - Klein, Ditte

AU - Sverrild, Asger

AU - Uller, Lena

PY - 2022

Y1 - 2022

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.

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.

U2 - 10.1183/13993003.02333-2021

DO - 10.1183/13993003.02333-2021

M3 - Journal article

C2 - 34916261

VL - 60

JO - The European Respiratory Journal

JF - The European Respiratory Journal

SN - 0903-1936

M1 - 2102333

ER -