Identification of a Novel Subset of Myeloid-Derived Suppressor Cells During Chronic Staphylococcal Infection That Resembles Immature Eosinophils

Abstract

We have previously reported that myeloid-derived suppressor cells (MDSC), which are a heterogeneous population of immunosuppressive immature myeloid cells, expanded during chronic Staphylococcus aureus infection and promoted bacterial persistence by inhibiting effector T cells. Two major MDSC subsets, including monocytic MDSC and granulocytic MDSC, have been described to date. Here, we identified a new subset of MDSC (Eo-MDSC) in S. aureus-infected mice that phenotypically resembles eosinophils. Eo-MDSC exhibit eosinophilic cytoplasmic granules and express CD11b, the eosinophil marker Syglec-F, variable levels of CCR3, and low levels of interleukin-5Rα. Furthermore, Eo-MDSC accumulated at the site of infection and exerted a potent immunosuppressive effect on T-cell responses that was mediated by nitric oxide-dependent depletion of l-arginine. Increases in the number of Eo-MDSC by adoptive transfer caused a significant exacerbation of infection in S. aureus-infected mice. This study sheds new light on the heterogeneity and complexity of MDSC during chronic infection.

Keywords: Staphylococcus aureus; chronic infection; eosinophils; immunosuppression; myeloid-derived suppressor cells.