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Influenza A virus (IAV) and SARS-CoV2 are known to disrupt pulmonary homeostasis, the mechanisms by which these perturbations render the host susceptibility to\n                  <jats:italic>Aspergillus fumigatus (Af)<\/jats:italic>\n                  remain incompletely understood. Here, we integrate an established murine model of influenza-associated pulmonary aspergillosis (IAPA) with single-cell RNA sequencing (scRNA-seq) to define the myeloid cell dysfunction that underlies IAPA establishment and progression.\n                <\/jats:p>\n                <jats:p>\n                  Single-cell transcriptomic profiling of pulmonary monocytes and macrophages revealed that IAV-\n                  <jats:italic>Af<\/jats:italic>\n                  coinfection drives a marked shift away from interferon-mediated antiviral and antigen presentation programs toward stress-associated and redox-regulatory transcriptional states. Pathway analyses demonstrated coordinated suppression of phagocytic and interferon signaling pathways alongside enrichment of oxidative stress and mitochondrial metabolic signatures \u2013 changes that closely recapitulate transcriptional defects previously reported in human IAPA patients. Myeloid cells from IAV-\n                  <jats:italic>Af<\/jats:italic>\n                  coinfected mice further exhibited increased oxidative phosphorylation alongside reduced glycolytic and phagocytic activity, consistent with impaired antifungal effector function.\n                <\/jats:p>\n                <jats:p>\n                  To elucidate how prior IAV infection generates a pulmonary microenvironment permissive to\n                  <jats:italic>Af<\/jats:italic>\n                  growth, we evaluated airway iron availability \u2013 a critical determinant of both fungal pathogenicity and immune regulation. IAV infection alone produced a significant elevation in bronchoalveolar iron levels accompanied by induction of iron-associated inflammatory mediators. Paradoxically, during IAV-\n                  <jats:italic>Af<\/jats:italic>\n                  coinfection, myeloid cells displayed markedly reduced expression of iron-sequestering and storage genes, revealing a fundamental disconnect between iron burden and cellular iron-handling capacity. Functionally, elevated iron accelerated\n                  <jats:italic>Af<\/jats:italic>\n                  germination and impaired macrophage-mediated fungal killing. Collectively, these findings identify IAV-induced pulmonary iron accumulation as a key driver of immunometabolic reprogramming in myeloid cells, resulting in compromised antifungal immunity and heightened susceptibility to secondary\n                  <jats:italic>Af<\/jats:italic>\n                  infection.\n                <\/jats:p>","DOI":"10.64898\/2026.04.22.720189","type":"posted-content","created":{"date-parts":[[2026,4,26]],"date-time":"2026-04-26T06:30:19Z","timestamp":1777185019000},"source":"Crossref","is-referenced-by-count":1,"title":["Myeloid Cell States in Influenza-Associated Pulmonary Aspergillosis Are Shaped by Iron Overload and Metabolic Reprogramming"],"prefix":"10.64898","author":[{"given":"Madeleine S.","family":"Grau","sequence":"first","affiliation":[{"name":"Geisel School of Medicine at Dartmouth, Department of Microbiology & Immunology, Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian P.","family":"Jackson","sequence":"additional","affiliation":[{"name":"Dartmouth College, Department of Earth and Planetary Sciences, Hanover, NH 03755"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carol","family":"Ringelberg","sequence":"additional","affiliation":[{"name":"Geisel School of Medicine at Dartmouth, Dartmouth Cancer Center, Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fred W.","family":"Kolling","sequence":"additional","affiliation":[{"name":"Geisel School of Medicine at Dartmouth, Dartmouth Cancer Center, Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"George S.","family":"Deepe","sequence":"additional","affiliation":[{"name":"University of Cincinnati College of Medicine, Division of Infectious Diseases, Cincinnati, OH 45267"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"Cramer","sequence":"additional","affiliation":[{"name":"Geisel School of Medicine at Dartmouth, Department of Microbiology & Immunology, Lebanon, NH 03756"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4068-7911","authenticated-orcid":false,"given":"Joshua J.","family":"Obar","sequence":"additional","affiliation":[{"name":"Geisel School of Medicine at Dartmouth, Department of Microbiology & Immunology, Lebanon, NH 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