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We integrated high-resolution single-cell RNA sequencing, spatial transcriptomics, quantitative immunofluorescence imaging, and cell-cell communication analyses to profile murine lungs across na\u00efve, asthma, influenza (flu), and co-morbid asthma and flu (asthma + flu) conditions. We identified 3 related EOS transcriptional states distributed along a disease-associated continuum. EOS in the flu-only condition preferentially expressed canonical antiviral and interferon-stimulated genes, including Isg15, Gbp2, and Samhd1, whereas asthma + flu EOS had attenuated induction of these programs together with enrichment of genes associated with chemotaxis, adhesion, inflammatory regulation, and metabolic remodeling. Asthma + flu EOS were also enriched for a human asthma-associated high EOS gene signature. A progressive shift in EOS from antigen-presenting programs toward chemotactic and tissue remodeling-associated states, as identified by pseudotime analysis, may imply a changing functional emphasis rather than sustained canonical antiviral activation. Spatial profiling confirmed condition-dependent EOS abundance, increased EOS Alox15 expression in allergic conditions, and disease-specific cellular neighborhoods. Cross-platform analyses identified recurrent predicted interactions between EOS and a distinct Alox15+ alveolar macrophage population. Mast cells adopted infection-specific interleukin-1 and leukocyte-activation transcriptional programs without major compositional changes. Collectively, these findings demonstrate that the type 2 microenvironment reshapes both the transcriptional state and spatial organization of lung EOS during IAV infection, providing an integrated framework for understanding EOS heterogeneity and cellular coordination in the allergic lungs.<\/jats:p>","DOI":"10.1093\/jleuko\/qiag120","type":"journal-article","created":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T13:51:46Z","timestamp":1788616306000},"source":"Crossref","is-referenced-by-count":0,"title":["Single-cell and spatial transcriptomics define eosinophil heterogeneity during influenza A virus\u2013induced exacerbation of fungal allergic asthma in C57BL\/6 mice"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7067-1796","authenticated-orcid":false,"given":"Anthony J","family":"Veltri","sequence":"first","affiliation":[{"name":"Biotechnology Center, University of Wisconsin-Madison , 425 Henry Mall, Madison, WI 53706 ,","place":["United 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