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Their effects are highly context-dependent and can be protective or pathological according to IFN class and ligand, cellular source and target, and the timing and duration of signaling. In this minireview, we compare the induction of type I, II, and III IFNs during respiratory viral infection and pulmonary\n                      <jats:italic toggle=\"yes\">Aspergillus fumigatus<\/jats:italic>\n                      infection, highlighting epithelial-led antiviral sensing and predominantly myeloid-centered antifungal sensing. We then examine how receptor distribution, ligand identity, JAK-STAT complex assembly, and integration with inflammatory pathways generate cell type-specific transcriptional and functional programs. Finally, we discuss three interconnected consequences of IFN crosstalk at the respiratory barrier: regulation of epithelial permeability and repair, licensing or pathological reprogramming of immune effector cells during primary infection, and loss of coordination during viral-fungal coinfection, including influenza-associated and COVID-19-associated pulmonary aspergillosis. Collectively, the available evidence supports a model in which spatially restricted and appropriately timed IFN responses promote pathogen control and preserve barrier function, whereas excessive, prolonged, or mistimed signaling impairs epithelial recovery, disrupts phagocyte activity, and increases susceptibility to secondary fungal invasion. Defining these context-dependent circuits may guide therapeutic strategies that modulate IFN signaling with greater temporal and cell type specificity.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/iai.00295-26","type":"journal-article","created":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:29:55Z","timestamp":1788366595000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":0,"title":["Interferon crosstalk at the lung barrier in viral and fungal infection"],"prefix":"10.1128","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3206-1804","authenticated-orcid":true,"given":"Maria","family":"Velez-Brochero","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05vt9qd57","id-type":"ROR","asserted-by":"publisher"}],"name":"Graduate School of Biomedical Sciences, New Jersey Medical School, Rutgers University","place":["Newark, 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