{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,10]],"date-time":"2026-01-10T22:24:22Z","timestamp":1768083862754,"version":"3.49.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012784","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,3,31]],"date-time":"2025-03-31T00:00:00Z","timestamp":1743379200000}}],"reference-count":83,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T00:00:00Z","timestamp":1738627200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["097377\/z\/11\/z"],"award-info":[{"award-number":["097377\/z\/11\/z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000292","name":"Cystic Fibrosis Trust","doi-asserted-by":"publisher","award":["SRC015"],"award-info":[{"award-number":["SRC015"]}],"id":[{"id":"10.13039\/501100000292","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["219551\/z\/19\/z"],"award-info":[{"award-number":["219551\/z\/19\/z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/V037315\/1"],"award-info":[{"award-number":["MR\/V037315\/1"]}],"id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Aspergillus fumigatus<\/jats:italic> (<jats:italic>Af<\/jats:italic>) is a major mould pathogen found ubiquitously in the air. It commonly infects the airways of people with cystic fibrosis (CF) leading to <jats:italic>Aspergillus<\/jats:italic> bronchitis or allergic bronchopulmonary aspergillosis. Resident alveolar macrophages and recruited neutrophils are important first lines of defence for clearance of <jats:italic>Af<\/jats:italic> in the lung. However, their contribution to the inflammatory phenotype in CF during <jats:italic>Af<\/jats:italic> infection is not well understood. Here, utilising CFTR deficient mice we describe a hyperinflammatory phenotype in both acute and allergic murine models of pulmonary aspergillosis. We show that during aspergillosis, CFTR deficiency leads to increased alveolar macrophage death and persistent inflammation of the airways in CF, accompanied by impaired fungal control. Utilising CFTR deficient murine cells and primary human CF cells we show that at a cellular level there is increased activation of NF\u03baB and NFAT in response to <jats:italic>Af<\/jats:italic> which, as in <jats:italic>in vivo<\/jats:italic> models, is associated with increased cell death and reduced fungal control. Taken together, these studies indicate that CFTR deficiency promotes increased activation of inflammatory pathways, the induction of macrophage cell death and reduced fungal control contributing to the hyper-inflammatory of pulmonary aspergillosis phenotypes in CF.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012784","type":"journal-article","created":{"date-parts":[[2025,2,4]],"date-time":"2025-02-04T18:38:58Z","timestamp":1738694338000},"page":"e1012784","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["Increased NFAT and NF\u03baB signalling contribute to the hyperinflammatory phenotype in response to Aspergillus fumigatus in a mouse model of cystic fibrosis"],"prefix":"10.1371","volume":"21","author":[{"given":"Amelia","family":"Bercusson","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1201-2944","authenticated-orcid":true,"given":"Thomas J.","family":"Williams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicholas J.","family":"Simmonds","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric WFW","family":"Alton","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Uta","family":"Griesenbach","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anand","family":"Shah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Adilia","family":"Warris","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1014-7343","authenticated-orcid":true,"given":"Darius","family":"Armstrong-James","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,2,4]]},"reference":[{"issue":"2","key":"ppat.1012784.ref001","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1128\/CMR.12.2.310","article-title":"Aspergillus fumigatus and aspergillosis","volume":"12","author":"JP 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