Selasa , 21 Des 2021 09:37:19
Phenotype and severity of asthma determines bronchial epithelial immune responses to a viral mimic


Celeste Porsbjerg, Juan Jose Nieto-Fontarigo, Samuel Cerps, Sangheeta Ramu, Mandy Menzel, Morten Hvidtfeldt, Alexander Silberbrandt, Laurits Froessing, Ditte Klein, Asger Sverrild, Lena Uller

European Respiratory Journal 2021; DOI: 10.1183/13993003.02333-2021

Abstract

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 virus 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) (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.

Results Patients 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.

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.

Footnotes

This 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: Prof. Celeste Porsbjerg declares having received honoraria as a speaker and consultant, and unrestricted research grants from AZ, GSK, Novartis, Sanofi, TEVA, Chiesi and Pharmaxis.

Conflict of interest: Juan Jose Nieto-Fontarigo has nothing to disclose.

Conflict of interest: Samuel Cerps has nothing to disclose.

Conflict of interest: Sangheeta Ramu has nothing to disclose.

Conflict of interest: Mandy Menzel has nothing to disclose.

Conflict of interest: Morten Hvidtfeldt has nothing to disclose.

Conflict of interest: Alexander Silberbrandt has nothing to disclose.

Conflict of interest: Laurits Froessing has nothing to disclose.

Conflict of interest: Ditte Klein has nothing to disclose.

Conflict of interest: Dr Asger Sverrild declares having received honoraria as a speaker and consultant, and unrestricted research grants AZ, Novartis, Sanofi and Chiesi.

Conflict of interest: Lena Uller has nothing to disclose.

  • Received August 25, 2021.
  • Accepted November 24, 2021.