The Interferon Response in Bronchiectasis

Abstract

Bronchiectasis is a chronic respiratory condition characterised by irreversible dilation of the bronchi, leading to recurrent respiratory infections and chronic inflammation. Bacterial infections have been well-recognised as potent inducers of exacerbations for decades. However, recent studies have indicated that viruses are present in up to 50% of exacerbations, raising questions of the role viruses play in bronchiectasis and triggering exacerbations. Despite evidence of their presence, the role of viruses in bronchiectasis remains largely underexplored. In other chronic lung conditions such as asthma and COPD, viruses have been proven to trigger exacerbations in patients and studies have
also shown patients to have deficiencies in the interferon response, a crucial part of the immune system in response to viral infections. Based on this we hypothesised that bronchiectasis patients may have an impaired interferon response to viral infections, increasing their risk of exacerbations.

To investigate this, we stimulated bronchiectasis patient and healthy PBMCs and nasal epithelial cells with Poly I:C, a viral mimic and measured interferon production using a sandwich immunoassay coupled with electrochemiluminescence via MSD plates. Our results showed no significant differences in the interferon levels between the two groups and analysis of clinical parameters did not identify a subgroup of patients predisposed to dampened interferon responses.

Additionally, we hypothesised that sputum samples from bronchiectasis patients experiencing viral exacerbations would exhibit higher interferon levels compared to nonviral exacerbations. We investigated this by measuring interferon concentrations in sputum samples using MSD plates and comparing the two groups. IFN-α2a and IFN-γ were significantly increased in the virus-positive group, but large heterogeneity of responses suggests there may be some subgroups with differences in response.

In conclusion, we identified viruses as an important trigger for bronchiectasis
exacerbations. Patients with viral exacerbations have an increased IFN-α2a and IFN-γ response, with high individual heterogeneity in response. In vitro we saw no differences between bronchiectasis and control subjects’ responses to Poly I:C stimulation.

Date of Award	2025
Original language	English
Awarding Institution	University of Dundee
Supervisor	James Chalmers (Supervisor) & Amelia Shoemark (Supervisor)