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Influenza infections in asthma patients can cause severe exacerbations, though the underlying mechanisms remain unclear. This study investigated how pre-existing allergic inflammation affects immune responses to influenza infection in mice exposed to house dust mite (HDM). Mice were repeatedly exposed to HDM, followed by infection with the influenza A virus, and were sacrificed three days post-infection. Plasma was analyzed for HDM-specific immunoglobulins, while lung tissue was used for immune cell flow cytometry and RNA sequencing analysis. HDM exposure induced allergic inflammation, evidenced by more HDM-specific IgE, IgG1, IgG2, eosinophils, neutrophils, Th1, and Th17 cells compared to controls. Upon influenza infection, the effects of HDM and influenza co-infection interacted, showing fewer Th1 cells and regulatory T cells and more Th2 cells compared to mice exposed to the influenza virus alone. Interestingly, RNA-seq analysis revealed less upregulation of Th1-related genes and antiviral pathways in co-exposed mice, suggesting impaired Th1 immunity and antiviral responses. Pre-existing allergic inflammation significantly altered immune responses in mice co-infected with influenza, revealing underdeveloped antiviral responses as early as three days post-infection. These findings may explain the increased susceptibility of patients with asthma to severe viral diseases.<\/jats:p>","DOI":"10.3390\/ijms26083483","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T03:32:53Z","timestamp":1744169573000},"page":"3483","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Pre-Existing Allergic Inflammation Alters Both Innate and Adaptive Immune Responses in Mice Co-Infected with Influenza Virus"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-3035-3461","authenticated-orcid":false,"given":"Dan","family":"Li","sequence":"first","affiliation":[{"name":"Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. Anienke","family":"van der Veen","sequence":"additional","affiliation":[{"name":"Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linsey E. S.","family":"de Groot","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina H.","family":"de Jager","sequence":"additional","affiliation":[{"name":"Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2260-1894","authenticated-orcid":false,"given":"Andy","family":"Lan","sequence":"additional","affiliation":[{"name":"Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hoeke A.","family":"Baarsma","sequence":"additional","affiliation":[{"name":"Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6243-9911","authenticated-orcid":false,"given":"Ren\u00e9","family":"Lutter","sequence":"additional","affiliation":[{"name":"Department of Respiratory Medicine, Amsterdam UMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kees","family":"van der Graaf","sequence":"additional","affiliation":[{"name":"Citeq Biologics BV, 9726 GN Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5595-152X","authenticated-orcid":false,"given":"Reinoud","family":"Gosens","sequence":"additional","affiliation":[{"name":"Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3075-0630","authenticated-orcid":false,"given":"Martina","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7091-907X","authenticated-orcid":false,"given":"Barbro N.","family":"Melgert","sequence":"additional","affiliation":[{"name":"Groningen Research Institute of Pharmacy, Department of Molecular Pharmacology, University of Groningen, 9713 AV Groningen, The Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD (GRIAC), University Medical Center Groningen, University of Groningen, 9713 AV Groningen, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,8]]},"reference":[{"key":"ref_1","unstructured":"Global Asthma Network (2025, February 13). 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