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Here, we define the pDC activation trajectory during A. fumigatus infection and the molecular events that underlie the protective pDC - neutrophil crosstalk. Fungus-induced pDC activation begins after bone marrow egress and results in pDC-dependent regulation of lung type I and type III IFN levels. These pDC-derived products act on type I and type III IFN receptor-expressing neutrophils and control neutrophil fungicidal activity and reactive oxygen species production via STAT1 signaling in a cell-intrinsic manner. Mechanistically, neutrophil STAT1 signaling regulates the transcription and expression of Cybb, which encodes one of five NADPH oxidase subunits. Thus, pDCs regulate neutrophil-dependent immunity against inhaled molds by controlling the local expression of a subunit required for NADPH oxidase assembly and activity in the lung.<\/jats:p>","DOI":"10.1101\/2024.10.24.620079","type":"posted-content","created":{"date-parts":[[2024,10,26]],"date-time":"2024-10-26T03:30:15Z","timestamp":1729913415000},"source":"Crossref","is-referenced-by-count":2,"title":["An IFN-STAT1-CYBB Axis Defines Protective Plasmacytoid DC to Neutrophil Crosstalk During Aspergillus fumigatus Infection."],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1587-4619","authenticated-orcid":false,"given":"Yahui","family":"Guo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2462-438X","authenticated-orcid":false,"given":"Mariano 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