{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:57:53Z","timestamp":1790740673718,"version":"4.1.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013418","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T00:00:00Z","timestamp":1775779200000}}],"reference-count":84,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["K08 AI130366"],"award-info":[{"award-number":["K08 AI130366"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01 AI162765"],"award-info":[{"award-number":["R01 AI162765"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006108","name":"National Center for Advancing Translational Sciences","doi-asserted-by":"publisher","award":["UL1TR001881"],"award-info":[{"award-number":["UL1TR001881"]}],"id":[{"id":"10.13039\/100006108","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    <jats:italic>Cryptococcus gattii<\/jats:italic>\n                    is an emerging fungal pathogen that is acquired through the respiratory tract and causes invasive infections in both immunocompromised and otherwise healthy people. Many of these apparently immunocompetent patients are subsequently found to have autoantibodies against the pleiotropic cytokine GM-CSF. In this study, we investigated the potential role of GM-CSF (or CSF2) in the host response to\n                    <jats:italic>C. gattii<\/jats:italic>\n                    using a murine model of infection. Interestingly, infected\n                    <jats:italic>Csf2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>-\/-<\/jats:italic>\n                    <\/jats:sup>\n                    mice were found to have significantly improved survival and decreased lung fungal burden compared to wild type (WT) mice. We determined that during\n                    <jats:italic>C. gattii<\/jats:italic>\n                    infection, GM-CSF promotes the differentiation of monocytes into alveolar and interstitial macrophages. When these macrophages are ablated in CCR2-DTR\n                    <jats:sup>+<\/jats:sup>\n                    mice, there is a corresponding improvement in survival with decreased lung fungal burden, thus phenocopying\n                    <jats:italic>Csf2<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>-\/-<\/jats:italic>\n                    <\/jats:sup>\n                    mice. WT bone-marrow derived macrophages challenged with\n                    <jats:italic>C. gattii<\/jats:italic>\n                    and interstitial and alveolar macrophages from infected WT mice are unable to undergo M1 polarization, suggesting that monocyte-derived macrophages (moMacs) are rendered permissive for fungal proliferation. Therefore, GM-CSF and moMacs mediate immune responses that are harmful to the host. We further found that GM-CSF and moMacs preferentially promote the influx of eosinophils over neutrophils into the infected lung which is associated with substantial inflammatory lung pathology. Ablation of neutrophils using Mrp8cre\n                    <jats:sup>tg<\/jats:sup>\n                    iDTR\n                    <jats:sup>+<\/jats:sup>\n                    mice significantly increased\n                    <jats:italic>C. gattii<\/jats:italic>\n                    burden in the lungs, indicating that GM-CSF and moMacs block the entry of these beneficial, fungal-clearing granulocytes during infection. Altogether, our results show that GM-CSF plays a key role in impeding host anti-fungal responses to\n                    <jats:italic>C. gattii<\/jats:italic>\n                    by coordinating monocyte-derived macrophages and granulocyte activity and crosstalk.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013418","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T17:38:11Z","timestamp":1775583491000},"page":"e1013418","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":3,"title":["GM-CSF orchestrates monocyte and granulocyte responses to Cryptococcus gattii"],"prefix":"10.1371","volume":"22","author":[{"given":"Alison","family":"Ricafrente","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sreemoyee","family":"Acharya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuyi","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adiza","family":"Abass","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aelita","family":"Arshakyan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tyler J.","family":"Olson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Apurwa","family":"Trivedi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6655-575X","authenticated-orcid":true,"given":"Lena J.","family":"Heung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"ppat.1013418.ref001","doi-asserted-by":"crossref","DOI":"10.1128\/9781555816858","volume-title":"Cryptococcus: from human pathogen to model yeast","author":"J Heitman","year":"2010","edition":"1"},{"issue":"10","key":"ppat.1013418.ref002","first-page":"792","article-title":"Multispecies outbreak of cryptococcosis on southern Vancouver Island, British Columbia","volume":"43","author":"C Stephen","year":"2002","journal-title":"Can Vet 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