Document Type
Article
Journal Title
Infection and Immunity
Publication Date
2026
Volume
94
Abstract
Staphylococcus aureus is a leading cause of prosthetic joint infection (PJI) typified by biofilm formation. Anti-inflammatory granulocytic myeloid-derived suppressor cells (G-MDSCs) represent the main leukocyte population in a mouse model of S. aureus PJI, followed by neutrophils (PMNs), and macrophages (Mφs), which is also seen during human PJI. Defining how each leukocyte population responds to S. aureus biofilm vs planktonic bacteria could have important implications for how S. aureus evades immune detection to facilitate biofilm persistence. This study compared the kinetics of leukocyte death and relationship to mitochondrial ROS (mtROS) production following exposure to planktonic S. aureus or biofilm. Mφs were exquisitely sensitive to S. aureus biofilm with toxicity observed within 15 min following biofilm co-culture, whereas G-MDSCs and PMNs were more resilient, with appreciable survival out to 6 h. In contrast, G-MDSC viability was significantly decreased after extended exposure to planktonic S. aureus compared to PMNs and Mφs. Although leukocyte death coincided with increased mtROS production across all leukocyte populations, inhibiting mtROS had no impact on leukocyte survival following biofilm co-culture, suggesting alternative cell death triggers. Caspase-1-dependent pyroptosis was observed in PMNs, whereas Mφs and G-MDSCs were targeted by necrosis since an inhibitor of H2O2-induced necrosis improved cell survival of both populations, whereas programmed cell death inhibitors had no effect. These findings may account, in part, for the abundance of G-MDSCs and PMNs, but not Mφs, during PJI based on differential susceptibility to biofilm-induced cytotoxicity.
MeSH Headings
Biofilms, Staphylococcus aureus, Staphylococcal Infections, Animals, Mice, Neutrophils, Leukocytes, Reactive Oxygen Species, Macrophages, Humans, Coculture Techniques, Mitochondria
DOI Link
ISSN
1098-5522
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Brandquist, Nichole D. and Kielian, Tammy, "Differential Sensitivity of Leukocyte Populations to Staphylococcus aureus Biofilm" (2026). Journal Articles: Pathology and Microbiology. 122.
https://digitalcommons.unmc.edu/com_pathmicro_articles/122