Elucidating granulocytic myeloid-derived suppressor cell (G-MDSC) fate during S. aureus biofilm infection

ABSTRACT: Myeloid-derived suppressor cells (MDSCs) are pathologically activated immature myeloid cells with immunosuppressive activity that expand during chronic inflammation, such as cancer and prosthetic joint infection (PJI). MDSCs can be broadly separated into two populations based on surface marker expression and function, namely monocytic MDSCs (M-MDSCs) and granulocytic MDSCs (G-MDSCs). In cancer models, M-MDSCs have been reported to transition into tumor-associated macrophages and/or dendritic cells, whereas G-MDSCs are considered terminally differentiated with short half-lives. G-MDSCs are the most abundant leukocyte infiltrate during PJI; however, how this population is maintained in vivo and cellular heterogeneity is currently unknown. In this study, we identified a population of Ly6G+Ly6C+F4/80+MHCII+ MDSCs during PJI that displayed immunosuppressive properties ex vivo. We leveraged F4/80 and MHCII expression by these cells for further characterization using cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq), which revealed a distinct transcriptomic signature of this population. F4/80+MHCII+ MDSCs displayed gene signatures resembling G-MDSCs, neutrophils, and monocytes, but had increased expression of genes involved in cytokine response/production, inflammatory cell death, and mononuclear cell differentiation. To determine whether F4/80+MHCII+ MDSCs represented an alternative differentiation state of G-MDSCs, Ly6G+Ly6C+F4/80-MHCII- G-MDSCs from CD45.1 mice were adoptively transferred into CD45.2 recipients using a mouse model of PJI. A small percentage of transferred G-MDSCs acquired F4/80 and MHCII expression in vivo, suggesting some degree of plasticity in this population. Collectively, these results demonstrate a previously unappreciated phenotype of G-MDSCs during PJI, which suggests a novel granulocytic-to-monocytic transition of MDSC infiltrates.

ORGANISM(S): Mus musculus

PROVIDER: GSE248640 | GEO | 2023/12/04

REPOSITORIES: GEO