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Updated: Oct 12, 2025
A Three-dimensional Tissue Culture Model to Study Primary Human Bone Marrow and its Malignancies
Published on: March 8, 2014
In Vitro 3D Staphylococcus aureus Abscess Communities Induce Bone Marrow Cells to Expand into Myeloid-Derived
Marloes I Hofstee1,2, Anja Heider3, Sonja Häckel4
1AO Research Institute Davos, 7270 Davos, Switzerland.
Abstract:
Staphylococcus aureus is the main causative pathogen of subcutaneous, bone, and implant-related infections, forming structures known as staphylococcal abscess communities (SACs) within tissues that also contain immunosuppressive myeloid-derived suppressor cells (MDSCs). Although both SACs and MDSCs are present in chronic S. aureus infections, it remains unknown whether SACs directly trigger MDSC expansion. To investigate this, a previously developed 3D in vitro SAC model was co-cultured with murine and human bone marrow cells. Subsequently, it was shown that SAC-exposed human CD11blow/- myeloid cells or SAC-exposed murine CD11b+ Gr-1+ cells were immunosuppressive mainly by reducing absolute CD4+ and CD8α+ T cell numbers, as shown in T cell proliferation assays and with flow cytometry. Monocytic MDSCs from mice with an S. aureus bone infection also strongly reduced CD4+ and CD8α+ T cell numbers. Using protein biomarker analysis and an immunoassay, we detected in SAC-bone marrow co-cultures high levels of GM-CSF, IL-6, VEGF, IL-1β, TNFα, IL-10, and TGF-β. Furthermore, SAC-exposed neutrophils expressed Arg-1 and SAC-exposed monocytes expressed Arg-1 and iNOS, as shown via immunofluorescent stains. Overall, this study showed that SACs cause MDSC expansion from bone marrow cells and identified possible mediators to target as an additional strategy for treating chronic S. aureus infections.
Insights
Staphylococcal abscess communities (SACs) directly trigger the expansion of immunosuppressive myeloid-derived suppressor cells (MDSCs). These SACs promote chronic Staphylococcus aureus infections by reducing T cell numbers, indicating potential therapeutic targets.
Area of Science:
- Microbiology
- Immunology
- Infectious Diseases
Background:
- Staphylococcus aureus causes various infections, forming staphylococcal abscess communities (SACs) that contain immunosuppressive myeloid-derived suppressor cells (MDSCs).
- The direct link between SACs and MDSC expansion in chronic infections is not well understood.
Purpose of the Study:
- To investigate whether staphylococcal abscess communities (SACs) directly induce the expansion of myeloid-derived suppressor cells (MDSCs).
Main Methods:
- Co-culture of a 3D in vitro SAC model with murine and human bone marrow cells.
- Flow cytometry and T cell proliferation assays to assess T cell numbers and immunosuppressive activity.
- Protein biomarker analysis and immunoassay to detect cytokine levels.
Main Results:
- SAC-exposed myeloid cells exhibited immunosuppressive properties, reducing CD4+ and CD8α+ T cell numbers.
- Monocytic MDSCs from infected mice also suppressed T cell populations.
- Elevated levels of cytokines including GM-CSF, IL-6, VEGF, IL-1β, TNFα, IL-10, and TGF-β were detected.
- SAC-exposed neutrophils and monocytes expressed Arg-1, with monocytes also expressing iNOS.
Conclusions:
- Staphylococcal abscess communities (SACs) directly promote the expansion of myeloid-derived suppressor cells (MDSCs) from bone marrow cells.
- Identified key mediators and cellular markers associated with SAC-induced MDSC expansion.
- These findings suggest novel therapeutic targets for chronic Staphylococcus aureus infections.
