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  • 1 Helmholtz Centre for Infection Research, Braunschweig, Germany
  • 2 University of Bonn, Bonn, Germany
  • 3 Hannover Medical School, Hannover, Germany
  • 4 University of Tennessee Health Science Center, Memphis, USA
  • 5 University of Würzburg, Würzburg, Germany
  • + National Institute of Health, Bethesda, USA

Influenza A virus (IAV) infection causes an acute respiratory disease characterized by a strong inflammatory immune response and severe immunopathology. Proinflammatory mechanisms are well described in the murine IAV infection model, but less is known about the mechanisms leading to the resolution of inflammation. Here, we analyzed the contribution of CD11b+Ly6C++Ly6G cells to this process. An accumulation of CD11b+Ly6C++Ly6G cells within the lungs was observed during the course of IAV infection. Phenotypic characterization of these CD11b+Ly6C++Ly6G cells by flow cytometry and RNA-Seq revealed an activated phenotype showing both pro- and anti-inflammatory features, including the expression of inducible nitric oxide synthase (iNOS) by a fraction of cells in an IFN-γ-dependent manner. Moreover, CD11b+Ly6C++Ly6G cells isolated from lungs of IAV-infected animals displayed suppressive activity when tested in vitro, and iNOS inhibitors could abrogate this suppressive activity. Collectively, our data suggest that during IAV infection, CD11b+Ly6C++Ly6G cells acquire immunoregulatory function, which might contribute to the prevention of pathology during this life-threatening disease.

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