In Vitro 3D <i>Staphylococcus aureus</i> Abscess Communities Induce Bone Marrow Cells to Expand into Myeloid-Derived Suppressor Cells
<i>Staphylococcus aureus</i> 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 b...
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| Autores principales: | , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/9c002aee20ab48efa46220de3f3e0464 |
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| Sumario: | <i>Staphylococcus aureus</i> 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 <i>S. aureus</i> 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 CD11b<sup>low/−</sup> myeloid cells or SAC-exposed murine CD11b<sup>+</sup> Gr-1<sup>+</sup> cells were immunosuppressive mainly by reducing absolute CD4<sup>+</sup> and CD8α<sup>+</sup> T cell numbers, as shown in T cell proliferation assays and with flow cytometry. Monocytic MDSCs from mice with an <i>S. aureus</i> bone infection also strongly reduced CD4<sup>+</sup> and CD8α<sup>+</sup> 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 <i>S. aureus</i> infections. |
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