Document Type
Article
Journal Title
Journal of Leukocyte Biology
Publication Date
2024
Volume
115
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). Myeloid-derived suppressor cells can be broadly separated into 2 populations based on surface marker expression and function: monocytic myeloid-derived suppressor cells (M-MDSCs) and granulocytic myeloid-derived suppressor cells (G-MDSCs). Granulocytic myeloid-derived suppressor cells 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 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, 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.
MeSH Headings
Myeloid-Derived Suppressor Cells, Staphylococcus aureus, Myeloid Cells, Monocytes, Biofilms
DOI Link
ISSN
1938-3673
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Bertrand, Blake P.; Heim, Cortney E.; Koepsell, Scott A.; and Kielian, Tammy, "Elucidating Granulocytic Myeloid-Derived Suppressor Cell Heterogeneity During Staphylococcus Aureus Biofilm Infection" (2024). Journal Articles: Pathology and Microbiology. 103.
https://digitalcommons.unmc.edu/com_pathmicro_articles/103