Gasdermin E is dispensable for H1N1 influenza virus pathogenesis in mice
Influenza virus infection activates multiple cell death pathways that shape disease outcomes. Here, we demonstrate that gasdermin E (GSDME)-mediated pyroptotic cell death does not significantly affect lung pathology or survival during severe H1N1 influenza virus infection. This finding contrasts with prior reports showing that GSDME worsens disease caused by H3N2 or H7N9 strains, as well as studies implicating gasdermin D in exacerbating H1N1 pathology. Thus, our data clarify that gasdermin family members contribute to influenza pathogenesis in a context-specific manner, underscoring the importance of considering viral diversity when evaluating the therapeutic potential of targeting cell death pathways.
Authors
- Samuel Speaks (ORCID: https://orcid.org/0009-0003-7610-1502)
- Adriana Forero (ORCID: https://orcid.org/0000-0002-2698-658X)
- Jonathan L. Papa
- Jacob S. Yount (ORCID: https://orcid.org/0000-0002-6128-4575)
- Steve Leumi (ORCID: https://orcid.org/0000-0002-8747-4051)
- Benjamin D. Liu (ORCID: https://orcid.org/0000-0002-2089-7607)
- Matthew I. McFadden (ORCID: https://orcid.org/0009-0005-4955-7111)
- Jana M. Cable (ORCID: https://orcid.org/0000-0001-9267-611X)
- Jack Roettger (ORCID: https://orcid.org/0009-0006-7584-3020)
- Brendan M. Reznik
- Shreenath Mohan
Institutions
- The Ohio State University Wexner Medical Center (US)
- The Ohio State University (US)
Publication Details
- Journal
- Microbiology Spectrum
- Published
- 2026-02-05
- DOI
- https://doi.org/10.1128/spectrum.02472-25
- Primary Topic
- Inflammasome and immune disorders
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- American Heart Association
- National Institutes of Health