{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T08:10:53Z","timestamp":1776759053379,"version":"3.51.2"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T00:00:00Z","timestamp":1665014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["PTDC\/MED-OUT\/1112\/2021, UIDB\/50026\/2020 , UIDP\/50026\/2020 , SFRH\/BD\/141127\/2018 , PD\/BD\/137680\/2018 , 2021.07836.BD , CEECIND\/00185\/2020 , CEECIND\/04058\/2018"],"award-info":[{"award-number":["PTDC\/MED-OUT\/1112\/2021, UIDB\/50026\/2020 , UIDP\/50026\/2020 , SFRH\/BD\/141127\/2018 , PD\/BD\/137680\/2018 , 2021.07836.BD , CEECIND\/00185\/2020 , CEECIND\/04058\/2018"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","award":["NORTE-01-0145-FEDER-000039, PPBI-POCI-01-0145-FEDER-022122"],"award-info":[{"award-number":["NORTE-01-0145-FEDER-000039, PPBI-POCI-01-0145-FEDER-022122"]}],"id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010676","name":"H2020 Societal Challenges","doi-asserted-by":"publisher","award":["847507"],"award-info":[{"award-number":["847507"]}],"id":[{"id":"10.13039\/100010676","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010434","name":"\u201cla Caixa\u201d Foundation","doi-asserted-by":"publisher","award":["LCF\/PR\/HR17\/52190003"],"award-info":[{"award-number":["LCF\/PR\/HR17\/52190003"]}],"id":[{"id":"10.13039\/100010434","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100017784","name":"Gilead Research Scholars","doi-asserted-by":"publisher","award":["Gilead Research Scholars Program - Antifungals"],"award-info":[{"award-number":["Gilead Research Scholars Program - Antifungals"]}],"id":[{"id":"10.13039\/100017784","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>Chronic pulmonary aspergillosis (CPA) is a devastating disease with increasing prevalence worldwide. The characteristic granulomatous-like inflammation poses as the major setback to effective antifungal therapies by limiting drug access to fungi. These inflammatory lung structures are reported to be severely hypoxic; nevertheless, the underlying mechanisms whereby these processes contribute to fungal persistence remain largely unknown. Hypoxia-inducible factor 1 alpha (HIF-1\u03b1), besides being the major cellular response regulator to hypoxia, is a known central immune modulator. Here, we used a model of <jats:italic>Aspergillus fumigatus<\/jats:italic> airway infection in myeloid-restricted HIF-1\u03b1 knock-out (<jats:italic>mHif1\u03b1<jats:sup>-\/-<\/jats:sup><\/jats:italic>) mice to replicate the complex structures resembling fungal granulomas and evaluate the contribution of HIF-1\u03b1 to antifungal immunity and disease development. We found that fungal-elicited granulomas in <jats:italic>mHif1\u03b1<jats:sup>-\/-<\/jats:sup><\/jats:italic> mice had significantly smaller areas, along with extensive hyphal growth and increased lung fungal burden. This phenotype was associated with defective neutrophil recruitment and an increased neutrophil death, therefore highlighting a central role for HIF-1\u03b1-mediated regulation of neutrophil function in the pathogenesis of chronic fungal infection. These results hold the promise of an improved capacity to manage the progression of chronic fungal disease and open new avenues for additional therapeutic targets and niches of intervention.<\/jats:p>","DOI":"10.3389\/fcimb.2022.1005839","type":"journal-article","created":{"date-parts":[[2022,10,6]],"date-time":"2022-10-06T12:48:39Z","timestamp":1665060519000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Hypoxia inducible-factor 1 alpha regulates neutrophil recruitment during fungal-elicited granulomatous inflammation"],"prefix":"10.3389","volume":"12","author":[{"given":"Sara","family":"da Silva-Ferreira","sequence":"first","affiliation":[]},{"given":"Cl\u00e1udio","family":"Duarte-Oliveira","sequence":"additional","affiliation":[]},{"given":"Daniela","family":"Antunes","sequence":"additional","affiliation":[]},{"given":"Catarina","family":"Barbosa-Matos","sequence":"additional","affiliation":[]},{"given":"Ana","family":"Mendes-Frias","sequence":"additional","affiliation":[]},{"given":"Eg\u00eddio","family":"Torrado","sequence":"additional","affiliation":[]},{"given":"Sandra","family":"Costa","sequence":"additional","affiliation":[]},{"given":"Ricardo","family":"Silvestre","sequence":"additional","affiliation":[]},{"given":"Cristina","family":"Cunha","sequence":"additional","affiliation":[]},{"given":"Agostinho","family":"Carvalho","sequence":"additional","affiliation":[]}],"member":"1965","published-online":{"date-parts":[[2022,10,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"100115","DOI":"10.1016\/j.simyco.2021.100115","article-title":"Aspergillus fumigatus and aspergillosis: From basics to clinics","volume":"100","author":"Arastehfar","year":"2021","journal-title":"Stud. 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