Monocytic myeloid-derived suppressor cells accumulate in the lungs of influenza A virus-infected mice. Mus musculus

Influenza A virus (IAV) infection causes an acute respiratory disease characterized by a strong inflammatory immune response and severe immunopathology. Pro-inflammatory 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 monocytic myeloid-derived suppressor cells (mono-MDSC) to this process. An accumulation of mono-MDSC within the lungs was observed during the course of IAV infection and phenotypic characterization of these mono-MDSC by flow cytometry and RNA-Seq revealed an activated phenotype showing both pro- and anti-inflammatory features, including the expression of iNOS by a fraction of cells in an IFN-g-dependent manner. Mono-MDSC 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 monocytes can differentiate into mono-MDSC, which might contribute to the prevention of immunopathology during this life-threatening disease. Overall design: Analysis of changes in the expression of mRNAs in three different groups