Document Type
Article
Journal Title
The Journal of Clinical Investigation
Publication Date
2-29-2024
Volume
134
Abstract
Staphylococcus aureus is a leading cause of biofilm-associated prosthetic joint infection (PJI). A primary contributor to infection chronicity is an expansion of granulocytic myeloid-derived suppressor cells (G-MDSCs), which are critical for orchestrating the antiinflammatory biofilm milieu. Single-cell sequencing and bioinformatic metabolic algorithms were used to explore the link between G-MDSC metabolism and S. aureus PJI outcome. Glycolysis and the hypoxia response through HIF1a were significantly enriched in G-MDSCs. Interfering with both pathways in vivo, using a 2-deoxyglucose nanopreparation and granulocyte-targeted Hif1a conditional KO mice, respectively, attenuated G-MDSC-mediated immunosuppression and reduced bacterial burden in a mouse model of S. aureus PJI. In addition, single-cell RNA-Seq (scRNA-Seq) analysis of granulocytes from PJI patients also showed an enrichment in glycolysis and hypoxia-response genes. These findings support the importance of a glycolysis/HIF1a axis in promoting G-MDSC antiinflammatory activity and biofilm persistence during PJI.
MeSH Headings
Humans, Mice, Animals, Myeloid-Derived Suppressor Cells, Staphylococcus aureus, Biofilms, Granulocytes, Hypoxia
DOI Link
ISSN
1558-8238
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Horn, Christopher M.; Arumugam, Prabhakar; Van Roy, Zachary; Heim, Cortney E.; Fallet, Rachel W.; Bertrand, Blake P.; Shinde, Dhananjay; Chittezham Thomas, Vinai; Romanova, Svetlana; Bronich, Tatiana K.; Hartman, Curtis; Garvin, Kevin; and Kielian, Tammy, "Granulocytic Myeloid-Derived Suppressor Cell Activity During Biofilm Infection is Regulated by a glycolysis/HIF1a Axis" (2024). Journal Articles: Pathology and Microbiology. 104.
https://digitalcommons.unmc.edu/com_pathmicro_articles/104