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Adv."],"published-print":{"date-parts":[[2026,1,2]]},"abstract":"<jats:p>\n                    Immunocompetent and experimentally accessible alveolar systems to study human respiratory diseases are lacking. Here, we developed a single-donor human induced pluripotent stem cell-derived lung-on-chip (iLoC) containing type II and I alveolar epithelial cells, vascular endothelial cells, and macrophages in a microfluidic device that mimic lung three-dimensional mechanical stretching and air-liquid interface. Imaging and single-cell RNA sequencing analysis revealed that the iLoC recapitulated cellular profiles present in the human distal lung. Infection of the iLoC with the human pathogen\n                    <jats:italic toggle=\"yes\">Mycobacterium tuberculosis<\/jats:italic>\n                    (Mtb) showed that both macrophages and epithelial cells were infected but not permissive to bacterial replication. Stochastically, large macrophage clusters containing necrotic macrophages supporting Mtb replication were observed. A genetically engineered autophagy-deficient iLoC revealed that after Mtb infection, macrophage necrosis was higher upon ATG14 deficiency without bacterial replication. Together, we report an autologous, genetically tractable human alveolar model to study lung diseases and therapies.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aea9874","type":"journal-article","created":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T18:58:31Z","timestamp":1767293911000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":12,"title":["Autologous human iPSC\u2013derived alveolus-on-chip reveals early pathological events of\n                    <i>Mycobacterium tuberculosis<\/i>\n                    infection"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5155-2257","authenticated-orcid":true,"given":"Chak Hon","family":"Luk","sequence":"first","affiliation":[{"name":"Host-Pathogen Interactions in Tuberculosis Laboratory, The Francis Crick Institute, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6702-8994","authenticated-orcid":true,"given":"Gabriel L.","family":"Conway","sequence":"additional","affiliation":[{"name":"Host-Pathogen Interactions in Tuberculosis Laboratory, The Francis Crick Institute, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8051-7867","authenticated-orcid":true,"given":"Kim Jee","family":"Goh","sequence":"additional","affiliation":[{"name":"Host-Pathogen Interactions in Tuberculosis Laboratory, The Francis Crick Institute, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9937-8545","authenticated-orcid":true,"given":"Antony","family":"Fearns","sequence":"additional","affiliation":[{"name":"Host-Pathogen Interactions in Tuberculosis Laboratory, The Francis Crick Institute, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6487-452X","authenticated-orcid":true,"given":"Irene Rodriguez","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Bioinformatics and Biostatistics Science and Technology Platform, The Francis Crick Institute, London NW1 1AT, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9141-3833","authenticated-orcid":true,"given":"Nathan J.","family":"Day","sequence":"additional","affiliation":[{"name":"Host-Pathogen Interactions in Tuberculosis Laboratory, The Francis Crick Institute, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalia","family":"Athanasiadi","sequence":"additional","affiliation":[{"name":"Host-Pathogen Interactions in Tuberculosis Laboratory, The Francis Crick Institute, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0180-6500","authenticated-orcid":true,"given":"Rocco","family":"D\u2019Antuono","sequence":"additional","affiliation":[{"name":"Crick Advanced Light Microscopy STP, The Francis Crick Institute, 1 Midland Road, NW1 1AT, London, UK."},{"name":"Department of Biomedical Engineering, School of Biological Sciences, University of Reading, Reading, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrica","family":"Pellegrino","sequence":"additional","affiliation":[{"name":"Host-Pathogen Interactions in Tuberculosis Laboratory, The Francis Crick Institute, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janick D.","family":"Stucki","sequence":"additional","affiliation":[{"name":"Alveolix AG, Swiss Organs-on-Chip Innovation, Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina","family":"Hobi","sequence":"additional","affiliation":[{"name":"Alveolix AG, Swiss Organs-on-Chip Innovation, Bern, Switzerland."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3199-0337","authenticated-orcid":true,"given":"Maximiliano G.","family":"Gutierrez","sequence":"additional","affiliation":[{"name":"Host-Pathogen Interactions in Tuberculosis Laboratory, The Francis Crick Institute, London, UK."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"221","reference":[{"key":"e_1_3_2_2_2","first-page":"1","article-title":"Inflammatory mechanisms in the lung","volume":"2","author":"Moldoveanu B.","year":"2009","unstructured":"B. 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