In this section
@article{Laverty:2026:10.1016/j.ebiom.2026.106131,
author = {Laverty, SL and Felton, I and Casey, M and Hopwood, B and Simmonds, N and Armstrong-James, D and Shah, A and Kelleher, P},
doi = {10.1016/j.ebiom.2026.106131},
journal = {EBioMedicine},
title = {CFTR modulators partially restore the epithelial interferome in Aspergillus infection to improve clinical outcome},
url = {http://dx.doi.org/10.1016/j.ebiom.2026.106131},
volume = {124},
year = {2026}
}
TY - JOUR
AB - BackgroundThe impact of CFTR modulator therapy on host immunity and outcomes in people with Cystic Fibrosis (CF)-related Aspergillus lung disease is poorly defined. We aimed to characterise fungal-relevant clinical outcomes post-CFTR modulators and assess effects on the Aspergillus-dependent Type I/III interferome.MethodsBiomarkers of Aspergillus-related lung disease (Aspergillus-specific IgE/IgG), anti-fungal and corticosteroid therapy were analysed in a retrospective cohort of people with CF pre and post Elexacaftor/Tezacaftor/Ivacaftor (ETI) modulator therapy. Homozygous F508del (CF) and CFTR TALEN-corrected bronchial epithelial cells (BECs) were challenged with Aspergillus conidia and hyphae in the presence or absence of ETI CFTR modulator therapy with bulk RNA transcriptomics and RT-PCR used to analyse Type I/III interferon genes. Effects of exogenous type I and III interferons on CF-neutrophil antifungal effector function was further characterised.FindingsCFTR modulator (ETI) therapy was associated with a significant reduction in Aspergillus biomarkers alongside use of corticosteroid and anti-fungal therapy. In vitro Aspergillus stimulation enriched the Type I/III interferome in CFTR-corrected BECs compared to CF BECs, with ETI therapy partially restoring type I/III interferon gene expression in CF BECs. Administration of exogenous IFNλ1 increased anti-fungal killing in CF neutrophils without increased reactive-oxygen species or neutrophil extracellular trap production.InterpretationCFTR modulators have led to improved clinical outcomes in CF related Aspergillus-related lung disease potentially due to partial restoration of the host antifungal epithelial type I/III interferon response. Exogenous IFNλ1 further improved antifungal killing capacity of CF-neutrophils presenting a plausible future therapeutic strategy.
AU - Laverty,SL
AU - Felton,I
AU - Casey,M
AU - Hopwood,B
AU - Simmonds,N
AU - Armstrong-James,D
AU - Shah,A
AU - Kelleher,P
DO - 10.1016/j.ebiom.2026.106131
PY - 2026///
SN - 2352-3964
TI - CFTR modulators partially restore the epithelial interferome in Aspergillus infection to improve clinical outcome
T2 - EBioMedicine
UR - http://dx.doi.org/10.1016/j.ebiom.2026.106131
VL - 124
ER -
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