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E Protein-Driven iNKT Subset Modulation Shapes Early Immune Responses during Influenza A Virus Infection.

ABSTRACT: IAV infection elicits a robust immune response including invariant natural killer T (iNKT) cells. Using mouse strains with normal iNKT numbers but altered subset representation (NKTWT vs NKTET-2), we show that NKTET-2 mice exhibit reduced weight loss, diminished neutrophil recruitment and inflammatory monocyte activation, and ~40% less HA+ infected lung area versus controls. Early lung expression of type I IFN–responsive genes (IFIT1, ISG15) and chemokines (CCL2, CXCL2) was lower in NKTET-2, whereas IFNλ was elevated. Single-cell RNA-seq of sorted lung iNKT cells revealed that NKTET-2 favored adhesion/repair and iNKT17-like programs over NKTWT type 1 effector responses. Modulating iNKT subset balance may limit immunopathology while preserving antiviral defense in IAV.

ORGANISM(S): Mus musculus

PROVIDER: GSE306684 | GEO | 2026/05/15

REPOSITORIES: GEO

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