{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T20:45:55Z","timestamp":1787863555312,"version":"build-2784847793"},"reference-count":39,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/100009689","name":"British Mycological Society","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009689","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/V031287\/1"],"award-info":[{"award-number":["MR\/V031287\/1"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007155","name":"Medical Research Council","doi-asserted-by":"publisher","award":["MR\/S024611"],"award-info":[{"award-number":["MR\/S024611"]}],"id":[{"id":"10.13039\/501100007155","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2025,11,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Human fungal pathogens, including\n                      <jats:italic toggle=\"yes\">Cryptococcus neoformans,<\/jats:italic>\n                      cause 1.5 million annual deaths.\n                      <jats:italic toggle=\"yes\">Cryptococcus<\/jats:italic>\n                      causes disease when it disseminates out of the lung and into the brain, which can occur years after initial exposure (latency) via mechanisms that remain unknown. Spores of\n                      <jats:italic toggle=\"yes\">Cryptococcus<\/jats:italic>\n                      display distinct surface epitopes, host interactions, and disease kinetics to the vegetatively growing yeast morphotype, yet they remain understudied, likely contributing to our lack of understanding of pathogenesis. One of the first barriers spores encounter is non-professional phagocytic\n                      <jats:underline>a<\/jats:underline>\n                      irway\n                      <jats:underline>e<\/jats:underline>\n                      pithelial\n                      <jats:underline>c<\/jats:underline>\n                      ells (AECs). Here, we demonstrate that\n                      <jats:italic toggle=\"yes\">Cryptococcus<\/jats:italic>\n                      spores are preferentially internalized by AECs both\n                      <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                      and\n                      <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                      . Once inside, spores can germinate, subsequently replicate, persist, and\/or escape. This ability to enter AECs correlates with a preferential ability of spores to cross AEC barriers. Together, our work indicates that AECs internalize\n                      <jats:italic toggle=\"yes\">Cryptococcus<\/jats:italic>\n                      spores and may serve as a previously ignored intracellular host niche, providing alternative hypotheses for both\n                      <jats:italic toggle=\"yes\">Cryptococcus<\/jats:italic>\n                      dissemination and latency.\n                    <\/jats:p>\n                    <jats:sec>\n                      <jats:title>IMPORTANCE<\/jats:title>\n                      <jats:p>\n                        Fungal spores are a dormant, stress-resistant, and relatively understudied cell type and are presumed infectious cell types in cryptococcal disease.\n                        <jats:italic toggle=\"yes\">Cryptococcus<\/jats:italic>\n                        spores have been shown to display distinct disease kinetics to the vegetative yeast morphotype and are significantly better at disseminating out of the host lung. While the molecular mechanisms by which spores disseminate out of the lung have yet to be identified, their preferential ability to get inside host cells likely enables their dissemination. Here, we show that spores, unlike yeast, readily get taken up by non-professional phagocytic cells, airway epithelial cells, both\n                        <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                        and\n                        <jats:italic toggle=\"yes\">in vivo,<\/jats:italic>\n                        and once inside can germinate, replicate, escape, and\/or persist. These results provide a previously unexplored host cell type that\n                        <jats:italic toggle=\"yes\">Cryptococcus<\/jats:italic>\n                        can inhabit, likely affecting disease kinetics and could be a critical interaction in understanding both extrapulmonary dissemination and latency.\n                      <\/jats:p>\n                    <\/jats:sec>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01831-25","type":"journal-article","created":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T13:09:22Z","timestamp":1761138562000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":2,"title":["<i>Cryptococcus<\/i>\n                    displays spore-specific uptake by alveolar epithelial cells"],"prefix":"10.1128","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4403-9519","authenticated-orcid":false,"given":"S\u00e9bastien C.","family":"Ortiz","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/027m9bs27","id-type":"ROR","asserted-by":"publisher"}],"name":"Manchester Fungal Infection Group, Faculty of Biology, Medicine and Health, The University of Manchester, Core Technology Facility","place":["Manchester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachael","family":"Fortune-Grant","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/027m9bs27","id-type":"ROR","asserted-by":"publisher"}],"name":"Manchester Fungal Infection Group, Faculty of Biology, Medicine and Health, The University of Manchester, Core Technology Facility","place":["Manchester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Thom","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/027m9bs27","id-type":"ROR","asserted-by":"publisher"}],"name":"Manchester Fungal Infection Group, Faculty of Biology, Medicine and Health, The University of Manchester, Core Technology Facility","place":["Manchester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua","family":"Davies","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/027m9bs27","id-type":"ROR","asserted-by":"publisher"}],"name":"Manchester Fungal Infection Group, Faculty of Biology, Medicine and Health, The University of Manchester, Core Technology Facility","place":["Manchester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5364-1838","authenticated-orcid":true,"given":"Robin C.","family":"May","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03angcq70","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Microbiology & Infection and School of Biosciences, University of Birmingham","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5424-7074","authenticated-orcid":true,"given":"Rebecca A.","family":"Drummond","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01x8c0495","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Immunology & Immunotherapy, Institute of Microbiology & Infection, University of Birmingham","place":["Birmingham, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5900-591X","authenticated-orcid":true,"given":"Margherita","family":"Bertuzzi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/027m9bs27","id-type":"ROR","asserted-by":"publisher"}],"name":"Manchester Fungal Infection Group, Faculty of Biology, Medicine and Health, The University of Manchester, Core Technology Facility","place":["Manchester, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.3390\/jof3040057"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3004404"},{"key":"e_1_3_3_4_2","unstructured":"World Health Organization. 2022. 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