{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:19:27Z","timestamp":1792790367036,"version":"4.5.0"},"posted":{"date-parts":[[2026,9,24]]},"group-title":"Immunology","reference-count":15,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"award":["F31 AI167511"],"award-info":[{"award-number":["F31 AI167511"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["P30 CA008748"],"award-info":[{"award-number":["P30 CA008748"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R37 AI093808"],"award-info":[{"award-number":["R37 AI093808"]}],"id":[{"id":"https:\/\/ror.org\/01cwqze88","id-type":"ROR","asserted-by":"publisher"}]},{"award":["882424"],"award-info":[{"award-number":["882424"]}],"id":[{"id":"https:\/\/ror.org\/0472cxd90","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Swiss National Science Foundation","award":["310030_170320"],"award-info":[{"award-number":["310030_170320"]}],"id":[{"id":"https:\/\/ror.org\/00yjd3n13","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Swiss National Science Foundation","award":["310030_188450"],"award-info":[{"award-number":["310030_188450"]}],"id":[{"id":"https:\/\/ror.org\/00yjd3n13","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Swiss National Science Foundation","award":["CRSII5_183478"],"award-info":[{"award-number":["CRSII5_183478"]}],"id":[{"id":"https:\/\/ror.org\/00yjd3n13","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01pd7my79","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,9,24]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                  is the most common cause of invasive aspergillosis (IA), an opportunistic pulmonary infection of immunocompromised patients that can be fatal, despite treatment with modern antifungal drugs. During infection, myeloid cells, such as neutrophils, monocytes, and monocyte-derived dendritic cells (Mo-DCs) are recruited to the lung and are critical for phagocytosing and killing\n                  <jats:italic>A. fumigatus<\/jats:italic>\n                  spores. Recent evidence has shown that intracellular crosstalk between these professional immune cells and other resident pulmonary cell types is required for an effective immune response to\n                  <jats:italic>A. fumigatus<\/jats:italic>\n                  , and that signaling via the cytokine granulocyte macrophage-colony stimulating factor (GM-CSF) is part of this intracellular communication. In this study, we sought to determine a role for GM-CSF signaling on monocytes and their progeny. We harnessed a mouse model of deletion of GM-CSF receptor \u03b2 chain (encoded by\n                  <jats:italic>Csf2rb<\/jats:italic>\n                  ) in CCR2-expressing cells. Using this model, we found that GM-CSF signaling is required on CCR2\n                  <jats:sup>+<\/jats:sup>\n                  cells for killing of\n                  <jats:italic>A. fumigatus<\/jats:italic>\n                  and for host survival. This observation expands the importance of GM-CSF in host defense during\n                  <jats:italic>A. fumigatus<\/jats:italic>\n                  pulmonary infection and extends its role in pathways of intracellular crosstalk that mediate effective pulmonary antifungal immunity.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>IMPORTANCE<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Aspergillus fumigatus<\/jats:italic>\n                    was recently designated a critical priority fungal pathogen by the World Health Organization due to its ability to cause fatal pulmonary disease and rapidly increasing acquired antifungal drug resistance. The mechanisms by which cells of the innate immune system cooperate to kill\n                    <jats:italic>A. fumigatus<\/jats:italic>\n                    spores in the lung are incompletely described and warrant further study so that these pathways may be manipulated in patients susceptible to infection. Here, we uncovered a role for the cytokine GM-CSF in coordinating crosstalk between lung epithelial cells and monocytes and monocyte-derived dendritic cells. GM-CSF signaling between these cells is required for fungal killing and host survival, expanding our understanding of the cell types involved in GM-CSF-mediated antifungal immunity.\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.09.22.753578","type":"posted-content","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:30:23Z","timestamp":1790296223000},"source":"Crossref","is-referenced-by-count":0,"title":["GM-CSF signaling on monocytes and monocyte-derived dendritic cells is required for effective pulmonary immunity to\n                  <i>Aspergillus fumigatus<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6476-1023","authenticated-orcid":false,"given":"Kathleen A. M.","family":"Mills","sequence":"first","affiliation":[{"name":"Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1541-7867","authenticated-orcid":false,"given":"Burkhard","family":"Becher","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology, University of Zurich, Zurich, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9097-5412","authenticated-orcid":false,"given":"Tobias M.","family":"Hohl","sequence":"additional","affiliation":[{"name":"Immunology and Microbial Pathogenesis Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA"},{"name":"Infectious Disease Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA"},{"name":"Immuno-Oncology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026092909001205000_2026.09.22.753578v1.1","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00140-18"},{"key":"2026092909001205000_2026.09.22.753578v1.2","doi-asserted-by":"publisher","DOI":"10.1038\/S41577-022-00826-W"},{"key":"2026092909001205000_2026.09.22.753578v1.3","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1016\/j.chom.2009.10.007","article-title":"Inflammatory Monocytes Facilitate Adaptive CD4 T Cell Responses during Respiratory Fungal Infection","volume":"6","year":"2009","journal-title":"Cell Host and Microbe"},{"key":"2026092909001205000_2026.09.22.753578v1.4","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003940"},{"key":"2026092909001205000_2026.09.22.753578v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2020.05.002"},{"key":"2026092909001205000_2026.09.22.753578v1.6","doi-asserted-by":"crossref","first-page":"eadr0547","DOI":"10.1126\/sciimmunol.adr0547","article-title":"GM-CSF\u2013mediated epithelial-immune cell cross-talk orchestrates pulmonary immunity to Aspergillus fumigatus","volume":"10","year":"2025","journal-title":"Science Immunology"},{"key":"2026092909001205000_2026.09.22.753578v1.7","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.4049\/jimmunol.2200430","article-title":"Cutting Edge: Neutrophils License the Maturation of Monocytes into Effective Antifungal Effectors","volume":"209","year":"2022","journal-title":"The Journal of Immunology"},{"key":"2026092909001205000_2026.09.22.753578v1.8","doi-asserted-by":"crossref","unstructured":"Gschwend J , Sherman SPM , Ridder F , Feng X , Liang HE , Locksley RM , Becher B , Schneider C. 2021. 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