CD11b ⁺Ly6C ⁺⁺Ly6G ^- Cells with Suppressive Activity Towards T Cells Accumulate in Lungs of Influenza a Virus-Infected Mice

Abstract

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.