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Animal models do not fully recapitulate human disease, necessitating advanced models to study human-fungal pathogen interactions. In this study, we utilized primary human airway epithelial cells (hAECs) to recapitulate the lung environment\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and investigate cellular responses to two diverse, clinically significant fungal pathogens,\n                      <jats:italic toggle=\"yes\">Aspergillus fumigatus<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">Coccidioides posadasii<\/jats:italic>\n                      . To understand the mechanisms of early pathogenesis for both fungi, we performed single-cell RNA sequencing of infected hAECs. Analysis revealed that both fungi induced cellular stress and cytokine production. However, the cellular subtypes affected and specific pathways induced differed between fungi, with\n                      <jats:italic toggle=\"yes\">A. fumigatus<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">C. posadasii<\/jats:italic>\n                      triggering protein-folding-related stress in ciliated cells and hypoxia responses in secretory cells, respectively. This study represents one of the first reports of single-cell transcriptional analysis of hAECs infected with either\n                      <jats:italic toggle=\"yes\">A. fumigatus<\/jats:italic>\n                      or\n                      <jats:italic toggle=\"yes\">C. posadasii<\/jats:italic>\n                      , providing a vital data set to dissect the mechanism of disease and potentially identify targetable pathways.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Fungal infections in the lungs are lethal complications for those with compromised immune systems and have limited treatment strategies available. These options are restricted further by the increased prevalence of treatment-resistant fungi. Many studies focus on how our immune systems respond to these pathogens, yet airway epithelial cells remain an understudied component of fungal infections in the lungs. Here, the authors provide a transcriptional analysis of primary human airway epithelial cells stimulated by two distinct fungal pathogens,\n                        <jats:italic toggle=\"yes\">Aspergillus fumigatus<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">Coccidioides posadasii<\/jats:italic>\n                        . These data will enable further mechanistic studies of the contribution of the airway epithelium to initial host responses and represent a powerful new resource for future investigations.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.02121-25","type":"journal-article","created":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T13:03:47Z","timestamp":1760360627000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":4,"title":["Single-cell analysis of human airway epithelium identifies cell-type-specific responses to\n                    <i>Aspergillus<\/i>\n                    and\n                    <i>Coccidioides<\/i>"],"prefix":"10.1128","volume":"16","author":[{"given":"Alfred T.","family":"Harding","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/042nb2s44","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Medical Engineering and Sciences, Massachusetts Institute of Technology","place":["Cambridge, USA"]},{"name":"Department of Microbiology, Harvard Medical School","place":["Cambridge, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arianne J.","family":"Crossen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/002pd6e78","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Infectious Diseases, Department of Medicine, Massachusetts General Hospital","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8979-3913","authenticated-orcid":false,"given":"Yanting","family":"Zhang","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/0558ewf28","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Environmental Health, Harvard T. 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