Journal article
Pseudomonas infections persisting after CFTR modulators are widespread throughout the lungs and drive lung inflammation
Cell host & microbe, Vol.33(8), pp.1428-1445.e4
07/31/2025
DOI: 10.1016/j.chom.2025.07.009
PMID: 40769150
Abstract
Cystic fibrosis transmembrane conductance regulator (CFTR) modulators improve the physiological defect causing cystic fibrosis, but the lungs of most people remain infected and inflamed. A leading hypothesis implicates damaged segments as the cause of persistent infection and predicts that mildly diseased segments within an individual's lungs will clear after treatment, whereas severely diseased segments will not. Our findings contradict this hypothesis. We used bronchoscopy to sample the least- and most-damaged lung segments in Pseudomonas aeruginosa (Pa)-infected individuals before modulators and returned to these same segments after 1.5 years. Surprisingly, we find an "all-or-none" infection clearance response: the most-diseased segments clear if any other lung segment in that person clears, and the least-diseased segments remain infected if others in that person do. Furthermore, neutrophilic inflammation completely resolves where Pa clears but remains elevated where Pa persists. These data indicate that post-modulator infections are not limited to severely diseased segments and that Pa infections drive persistent lung inflammation after modulators.
Details
- Title: Subtitle
- Pseudomonas infections persisting after CFTR modulators are widespread throughout the lungs and drive lung inflammation
- Creators
- Samantha L Durfey - University of WashingtonSiddhartha G Kapnadak - University of WashingtonTahuanty Pena - University of IowaMatthew M Willmering - Cincinnati Children's Hospital Medical CenterJ David Godwin - University of WashingtonMary E Teresi - University of IowaSonya L Heltshe - Cystic Fibrosis FoundationAnh T Vo - University of WashingtonRaul A Villacreses - University of IowaIeva Aliukonyte - Erasmus MC - Sophia Children’s HospitalLinda Boyken - University of IowaMal R Stroik - University of IowaSarah J Morgan - University of WashingtonGrace M Wang - University of WashingtonHannah L Betts - University of WashingtonShide Zhang - University of WashingtonChristopher H Goss - University of WashingtonJohn P Clancy - Cystic Fibrosis FoundationMoira L Aitken - University of WashingtonChad Steele - Tulane UniversityAlison F Feder - Fred Hutch Cancer CenterCharles R Esther JrHarm A W M Tiddens - Erasmus MC - Sophia Children’s HospitalJason C Woods - Cincinnati Children's Hospital Medical CenterDavid A Stoltz - University of IowaPradeep K Singh - University of Washington
- Resource Type
- Journal article
- Publication Details
- Cell host & microbe, Vol.33(8), pp.1428-1445.e4
- DOI
- 10.1016/j.chom.2025.07.009
- PMID
- 40769150
- NLM abbreviation
- Cell Host Microbe
- ISSN
- 1931-3128
- eISSN
- 1934-6069
- Publisher
- CELL PRESS; CAMBRIDGE
- Grant note
- CFFCystic Fibrosis Foundation (CFF): SINGH19KO National Institute of Health: R01HL160710, P30DK089507 NIH/NHLBI: P30DK065988 CFF: SINGH24R0, STOLTZ19R0, ESTHER22Y2-SVC, ES-THER24R0
We thank the people with CF and their families who participated in this study. We thank S. Lory, S. Salipante, and C. Manoil for helpful discussions. Neutrophil elastase assays were performed by the CFF-funded Center for Biochemical Markers at the University of Colorado Anschutz Medical Campus. This study was funded by the Cystic Fibrosis Foundation (CFF) grant SINGH19KO (to P.K.S.) . Additional funding that supported this research was provided by National Institute of Health grants R01HL160710 and P30DK089507 (to P.K. S.) and NIH/NHLBI P30DK065988 (to C.R.E.) and from CFF grants SINGH24R0 (to P.K.S.),STOLTZ19R0 (to D.A.S.), and ESTHER22Y2-SVC and ES-THER24R0 (to C.R.E.). Funding agencies had no role in the design, management, data collection, analyses, or interpretation of the data.
- Language
- English
- Date published
- 07/31/2025
- Academic Unit
- Molecular Physiology and Biophysics; Pulmonary, Critical Care, and Occupational Medicine; Stead Family Department of Pediatrics; Pathology; Internal Medicine
- Record Identifier
- 9984944727902771
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