Elucidating granulocytic myeloid-derived suppressor cell heterogeneity during Staphylococcus aureus biofilm infection

In this study, we identified a previously unknown 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 significantly increased expression of pathways involved in cytokine response/production, inflammatory cell death, and mononuclear cell differentiation. To determine whether F4/80 + MHCII+ MDSCs represented an alternate phenotypic 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 F4/80 + MHCII+ MDSCs during PJI, revealing that a granulocytic-to-monocytic transition can occur during biofilm infection.PMID:38095415 | DOI:10.1093/jleuko/qiad158
Source: Journal of Leukocyte Biology - Category: Hematology Authors: Source Type: research