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Updated: May 28, 2026

Modeling Dysplastic and Functional Lung Alveolar Repair after Influenza Infection
Published on: September 19, 2025
Pivotal Advance: Invariant NKT cells reduce accumulation of inflammatory monocytes in the lungs and decrease
Wai Ling Kok1, Laura Denney, Kambez Benam
1MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, Oxford University, Oxford, UK.
Abstract:
Little is known of how a strong immune response in the lungs is regulated to minimize tissue injury during severe influenza A virus (IAV) infection. Here, using a model of lethal, high-pathogenicity IAV infection, we first show that Ly6C(hi)Ly6G(-) inflammatory monocytes, and not neutrophils, are the main infiltrate in lungs of WT mice. Mice devoid of iNKT cells (Jα18(-/-) mice) have increased levels of inflammatory monocytes, which correlated with increased lung injury and mortality (but not viral load). Activation of iNKT cells correlated with reduction of MCP-1 levels and improved outcome. iNKT cells were able to selectively lyse infected, MCP-1-producing monocytes in vitro, in a CD1d-dependent process. Our study provides a detailed profile and kinetics of innate immune cells in the lungs during severe IAV infection, highlighting inflammatory monocytes as the major infiltrate and identifying a role for iNKT cells in control of these cells and lung immune-pathology.
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