In Vitro 3D Staphylococcus aureus Abscess Communities Induce Bone Marrow Cells to Expand into Myeloid-Derived Suppressor Cells
| Autor: | Sonja Häckel, Martijn Riool, Marloes I. Hofstee, Sebastian A. J. Zaat, T. Fintan Moriarty, R. Geoff Richards, Anja Heider, Caroline Constant |
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| Přispěvatelé: | Graduate School, AII - Infectious diseases, Medical Microbiology and Infection Prevention |
| Rok vydání: | 2021 |
| Předmět: |
staphylococcal abscess community
Microbiology (medical) Staphylococcus aureus T cell 610 Medicine & health host-pathogen interaction Biology medicine.disease_cause Article Flow cytometry Bone Infection myeloid-derived suppressor cell medicine bone infection Immunology and Allergy Molecular Biology General Immunology and Microbiology medicine.diagnostic_test In vitro 3D in vitro model Infectious Diseases medicine.anatomical_structure Myeloid-derived Suppressor Cell Cancer research Medicine Tumor necrosis factor alpha Bone marrow |
| Zdroj: | Hofstee, Marloes I; Heider, Anja; Häckel, Sonja; Constant, Caroline; Riool, Martijn; Richards, R Geoff; Moriarty, T Fintan; Zaat, Sebastian A J (2021). In Vitro 3D Staphylococcus aureus Abscess Communities Induce Bone Marrow Cells to Expand into Myeloid-Derived Suppressor Cells. Pathogens, 10(11) MDPI AG 10.3390/pathogens10111446 Pathogens Pathogens, Vol 10, Iss 1446, p 1446 (2021) Volume 10 Issue 11 Pathogens (Basel, Switzerland), 10(11):1446. MDPI AG |
| ISSN: | 2076-0817 |
| DOI: | 10.48350/164074 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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