{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T16:14:12Z","timestamp":1773764052400,"version":"3.50.1"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                      is a major airborne fungal pathogen that causes invasive aspergillosis in immunocompromised individuals. This study aims to elucidate the autophagic mechanisms activated following the internalization of\n                      <jats:italic>A. fumigatus<\/jats:italic>\n                      conidia in human bronchial epithelial cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Specifically, we investigated the role of ULK1 and the autophagic processes in Beas2B cells upon\n                      <jats:italic>A. fumigatus<\/jats:italic>\n                      conidia internalization. The Beas2B cell line was used to assess the protein expression of ULK1, phosphorylated ULK1, and LC3-I\/II via Western blotting. Autophagosome structures were examined using transmission electron microscopy. Gene silencing of ULK1 using siRNA and pharmacological inhibition with SBI-0206965 were performed. Secreted inflammatory cytokines were quantified using specific immunoassays.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      <jats:italic>A. fumigatus<\/jats:italic>\n                      conidia induced a time- and dose-dependent conversion of LC3-I to LC3-II, indicating autophagic activation resembling LC3-associated phagocytosis (LAP). ULK1 expression significantly increased post-infection, whereas genetic silencing of ULK1 reduced LC3-II conversion. Notably, common fungal polysaccharides and Dectin-1 did not influence this process, but the loss of complement receptor 3 (CR3) elevated both basal and conidia-induced autophagy, correlating with increased AMPK expression.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      This study reveals a novel ULK1-dependent autophagic response similar to LAP during\n                      <jats:italic>A. fumigatus<\/jats:italic>\n                      internalization, highlighting potential therapeutic targets for managing invasive aspergillosis in immunocompromised patients.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmicb.2026.1756294","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:18:59Z","timestamp":1773757139000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["ULK1 mediated autophagy in airway cells during Aspergillus infection"],"prefix":"10.3389","volume":"17","author":[{"given":"Fangyan","family":"Chen","sequence":"first","affiliation":[{"name":"Department for Disinfection and Infection Control, Chinese PLA Center for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rui","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department for Disinfection and Infection Control, Chinese PLA Center for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuqing","family":"Sun","sequence":"additional","affiliation":[{"name":"Department for Disinfection and Infection Control, Chinese PLA Center for Disease Control and Prevention","place":["Beijing, China"]},{"name":"Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yangxuan","family":"Lin","sequence":"additional","affiliation":[{"name":"Department for Disinfection and Infection Control, Chinese PLA Center for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Cui","sequence":"additional","affiliation":[{"name":"Department for Disinfection and Infection Control, Chinese PLA Center for Disease Control and Prevention","place":["Beijing, China"]},{"name":"Department of Respiratory and Critical Care Medicine, Beijing Youan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingya","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department for Disinfection and Infection Control, Chinese PLA Center for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingsong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department for Disinfection and Infection Control, Chinese PLA Center for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zelei","family":"Wang","sequence":"additional","affiliation":[{"name":"Department for Disinfection and Infection Control, Chinese PLA Center for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dingchen","family":"Li","sequence":"additional","affiliation":[{"name":"Department for Disinfection and Infection Control, Chinese PLA Center for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mandong","family":"Hu","sequence":"additional","affiliation":[{"name":"Department for Disinfection and Infection Control, Chinese PLA Center for Disease Control and Prevention","place":["Beijing, China"]},{"name":"National Center of Biomedical Analysis","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Han","sequence":"additional","affiliation":[{"name":"Department for Disinfection and Infection Control, Chinese PLA Center for Disease Control and Prevention","place":["Beijing, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,17]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"136520","DOI":"10.1016\/j.ijbiomac.2024.136520","article-title":"\u03b2-Glucan signalling stimulates NOX-2 dependent autophagy and LC-3 associated autophagy (LAP) pathway","volume":"282","author":"Ahmad","year":"2024","journal-title":"Int. J. Biol. Macromol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.1111\/j.1398-9995.2009.02315.x","article-title":"Nod1, Nod2 and Nalp3 receptors, new potential targets in treatment of allergic rhinitis?","volume":"65","author":"Bogefors","year":"2010","journal-title":"Allergy"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e70130","DOI":"10.1096\/fj.202402126R","article-title":"LC3-associated phagocytosis and human diseases: insights from mechanisms to therapeutic potential","volume":"38","author":"Chen","year":"2024","journal-title":"FASEB J."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1038\/s41598-023-28567-3","article-title":"Involvement of JNK signaling in Aspergillus fumigatus-induced inflammatory factors release in bronchial epithelial cells","volume":"13","author":"Cui","year":"2023","journal-title":"Sci. Rep."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"e428","DOI":"10.1016\/S1473-3099(23)00692-8","article-title":"Global incidence and mortality of severe fungal disease","volume":"24","author":"Denning","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aan5357","article-title":"Type III interferon is a critical regulator of innate antifungal immunity","volume":"2","author":"Espinosa","year":"2017","journal-title":"Sci. Immunol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1164\/rccm.202009-3400OC","article-title":"Occurrence of invasive pulmonary fungal infections in patients with severe COVID-19 admitted to the ICU","volume":"203","author":"Fekkar","year":"2021","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1955","DOI":"10.1038\/s41467-022-29580-2","article-title":"The crystal structure of iC3b-CR3 \u03b1I reveals a modular recognition of the main opsonin iC3b by the CR3 integrin receptor","volume":"13","author":"Fern\u00e1ndez","year":"2022","journal-title":"Nat. Commun."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1016\/S2213-2600(22)00259-4","article-title":"Lung epithelial and myeloid innate immunity in influenza-associated or COVID-19-associated pulmonary aspergillosis: an observational study","volume":"10","author":"Feys","year":"2022","journal-title":"Lancet Respir. Med."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.1038\/ncb2363","article-title":"Autophagy machinery mediates macroendocytic processing and entotic cell death by targeting single membranes","volume":"13","author":"Florey","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1080\/15548627.2022.2090727","article-title":"Stimulating the autophagic-lysosomal axis enhances host defense against fungal infection in a zebrafish model of invasive aspergillosis","volume":"19","author":"Forn-Cun\u00ed","year":"2023","journal-title":"Autophagy"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"324","DOI":"10.1016\/j.chom.2018.01.018","article-title":"The \u03b2(2) integrin mac-1 induces protective LC3-associated phagocytosis of Listeria monocytogenes","volume":"23","author":"Gluschko","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1980","DOI":"10.1080\/21505594.2021.1958042","article-title":"Complement receptor 3 mediates Aspergillus fumigatus internalization into alveolar epithelial cells with the increase of intracellular phosphatidic acid by activating FAK","volume":"12","author":"Han","year":"2021","journal-title":"Virulence"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"800","DOI":"10.3892\/ijmm.2017.3270","article-title":"Autophagy relieves the function inhibition and apoptosis-promoting effects on osteoblast induced by glucocorticoid","volume":"41","author":"Han","year":"2018","journal-title":"Int. J. Mol. Med."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1462","DOI":"10.1080\/15548627.2018.1475816","article-title":"LC3-associated phagocytosis initiated by integrin ITGAM-ITGB2\/mac-1 enhances immunity to Listeria monocytogenes","volume":"14","author":"Herb","year":"2018","journal-title":"Autophagy"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1038\/cdd.2016.140","article-title":"Global ischemia induces lysosomal-mediated degradation of mTOR and activation of autophagy in hippocampal neurons destined to die","volume":"24","author":"Hwang","year":"2017","journal-title":"Cell Death Differ."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1038\/s41420-019-0222-2","article-title":"Tomorou attenuates progression of rheumatoid arthritis through alteration in ULK-1 independent autophagy pathway in collagen induced arthritis mice model","volume":"5","author":"Jannat","year":"2019","journal-title":"Cell Death Discov."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"2216","DOI":"10.1038\/s41564-024-01780-0","article-title":"Manipulation of host phagocytosis by fungal pathogens and therapeutic opportunities","volume":"9","author":"Jia","year":"2024","journal-title":"Nat. Microbiol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1038\/ncb2152","article-title":"AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1","volume":"13","author":"Kim","year":"2011","journal-title":"Nat. Cell Biol."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"791","DOI":"10.1038\/s41564-018-0167-x","article-title":"Calcium sequestration by fungal melanin inhibits calcium-calmodulin signalling to prevent LC3-associated phagocytosis","volume":"3","author":"Kyrmizi","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"627","DOI":"10.1038\/mi.2017.100","article-title":"Differential regulation of the transcriptomic and secretomic landscape of sensor and effector functions of human airway epithelial cells","volume":"11","author":"Lehmann","year":"2018","journal-title":"Mucosal Immunol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1167\/iovs.61.2.25","article-title":"The role of autophagy in the innate immune response to fungal keratitis caused by Aspergillus fumigatus infection","volume":"61","author":"Li","year":"2020","journal-title":"Invest. Ophthalmol. Vis. Sci."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"435","DOI":"10.3390\/microorganisms9020435","article-title":"Bacterial interactions with Aspergillus fumigatus in the immunocompromised lung","volume":"9","author":"Margalit","year":"2021","journal-title":"Microorganisms"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"893","DOI":"10.1038\/ncb3192","article-title":"Molecular characterization of LC3-associated phagocytosis reveals distinct roles for Rubicon, NOX2 and autophagy proteins","volume":"17","author":"Martinez","year":"2015","journal-title":"Nat. Cell Biol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"796","DOI":"10.1080\/15548627.2019.1569297","article-title":"Macrophages target Salmonella by Lc3-associated phagocytosis in a systemic infection model","volume":"15","author":"Masud","year":"2019","journal-title":"Autophagy"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"728","DOI":"10.1016\/j.cell.2011.10.026","article-title":"Autophagy: renovation of cells and tissues","volume":"147","author":"Mizushima","year":"2011","journal-title":"Cell"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2018\/6195958","article-title":"Autophagy and LAP in the fight against fungal infections: regulation and therapeutics","volume":"2018","author":"Oikonomou","year":"2018","journal-title":"Mediat. Inflamm."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"eabn1702","DOI":"10.1126\/sciadv.abn1702","article-title":"Beyond autophagy: LC3-associated phagocytosis and endocytosis","volume":"8","author":"Pe\u00f1a-Martinez","year":"2022","journal-title":"Sci. Adv."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1562","DOI":"10.1128\/EC.00141-07","article-title":"Gliotoxin is a virulence factor of Aspergillus fumigatus: gliP deletion attenuates virulence in mice immunosuppressed with hydrocortisone","volume":"6","author":"Sugui","year":"2007","journal-title":"Eukaryot. Cell"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"4229","DOI":"10.1016\/j.jmb.2019.03.027","article-title":"Menacing Mold: recent advances in aspergillus pathogenesis and host defense","volume":"431","author":"Tischler","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e0209652","DOI":"10.1371\/journal.pone.0209652","article-title":"Transcriptomic and proteomic host response to Aspergillus fumigatus conidia in an air-liquid interface model of human bronchial epithelium","volume":"13","author":"Toor","year":"2018","journal-title":"PLoS One"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"155512","DOI":"10.1016\/j.phymed.2024.155512","article-title":"Shikonin suppresses rheumatoid arthritis by inducing apoptosis and autophagy via modulation of the AMPK\/mTOR\/ULK-1 signaling pathway","volume":"128","author":"Wang","year":"2024","journal-title":"Phytomedicine"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"1983","DOI":"10.4161\/auto.26058","article-title":"Regulation of PIK3C3\/VPS34 complexes by MTOR in nutrient stress-induced autophagy","volume":"9","author":"Yuan","year":"2013","journal-title":"Autophagy"}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1756294\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T14:19:00Z","timestamp":1773757140000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2026.1756294\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,17]]},"references-count":33,"alternative-id":["10.3389\/fmicb.2026.1756294"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2026.1756294","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,17]]},"article-number":"1756294"}}