{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:52:35Z","timestamp":1785433955669,"version":"3.56.0"},"posted":{"date-parts":[[2024,8,31]]},"group-title":"Microbiology","reference-count":60,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T00:00:00Z","timestamp":1725062400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"award":["U19 AI142784"],"award-info":[{"award-number":["U19 AI142784"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,27]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Lung disease due to non-tuberculous mycobacteria (NTM) is rising in incidence. While both two dimensional cell culture and animal models exist for NTM infections, a major knowledge gap is the early responses of human alveolar and innate immune cells to NTM within the human alveolar microenvironment. Here we describe development of a humanized, three-dimensional, alveolus lung-on-a-chip (ALoC) model of\n                  <jats:italic>Mycobacterium fortuitum<\/jats:italic>\n                  lung infection that incorporates only primary human cells such as pulmonary vascular endothelial cells in a vascular channel, and type I and II alveolar cells and monocyte-derived macrophages in an alveolar channel along an air-liquid interface.\n                  <jats:italic>M. fortuitum<\/jats:italic>\n                  introduced into the alveolar channel primarily infected macrophages, with rare bacteria inside alveolar cells. Bulk-RNA sequencing of infected chips revealed marked upregulation of transcripts for cytokines, chemokines and secreted protease inhibitors (SERPINs). Our results demonstrate how a humanized ALoC system can identify critical early immune and epithelial responses to\n                  <jats:italic>M. fortuitum<\/jats:italic>\n                  infection. We envision potential application of the ALoC to other NTM and for studies of new antibiotics.\n                <\/jats:p>","DOI":"10.1101\/2024.08.30.610530","type":"posted-content","created":{"date-parts":[[2024,8,31]],"date-time":"2024-08-31T22:30:12Z","timestamp":1725143412000},"source":"Crossref","is-referenced-by-count":2,"title":["An alveolus lung-on-a-chip model of\n                  <i>Mycobacterium fortuitum<\/i>\n                  lung infection"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1276-6563","authenticated-orcid":false,"given":"Victoria","family":"Ektnitphong","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7433-3869","authenticated-orcid":false,"given":"Beatriz R.S.","family":"Dias","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1789-3290","authenticated-orcid":false,"given":"Priscila C.","family":"Campos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4329-2253","authenticated-orcid":false,"given":"Michael U.","family":"Shiloh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025062901100815000_2024.08.30.610530v2.1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.2c00314"},{"key":"2025062901100815000_2024.08.30.610530v2.2","doi-asserted-by":"publisher","DOI":"10.1186\/s12941-023-00562-6"},{"key":"2025062901100815000_2024.08.30.610530v2.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1276-2"},{"key":"2025062901100815000_2024.08.30.610530v2.4","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-29562-4"},{"key":"2025062901100815000_2024.08.30.610530v2.5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0007083"},{"key":"2025062901100815000_2024.08.30.610530v2.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.isci.2024.111063"},{"key":"2025062901100815000_2024.08.30.610530v2.7","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1253037"},{"key":"2025062901100815000_2024.08.30.610530v2.8","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-pathol-012414-040418"},{"key":"2025062901100815000_2024.08.30.610530v2.9","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.3697"},{"key":"2025062901100815000_2024.08.30.610530v2.10","doi-asserted-by":"publisher","DOI":"10.1038\/nature09247"},{"key":"2025062901100815000_2024.08.30.610530v2.11","unstructured":"Bethencourt, M. 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