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In vitro 3D Staphylococcus aureus abscess communities induce bone marrow cells to expand into myeloid-derived suppressor cells. / Hofstee, Marloes I.; Heider, Anja; Häckel, Sonja et al.

In: Pathogens (Basel, Switzerland), Vol. 10, No. 11, 1446, 01.11.2021.

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Hofstee MI, Heider A, Häckel S, Constant C, Riool M, Richards RG et al. In vitro 3D Staphylococcus aureus abscess communities induce bone marrow cells to expand into myeloid-derived suppressor cells. Pathogens (Basel, Switzerland). 2021 Nov 1;10(11):1446. doi: 10.3390/pathogens10111446

Author

Hofstee, Marloes I. ; Heider, Anja ; Häckel, Sonja et al. / In vitro 3D Staphylococcus aureus abscess communities induce bone marrow cells to expand into myeloid-derived suppressor cells. In: Pathogens (Basel, Switzerland). 2021 ; Vol. 10, No. 11.

BibTeX

@article{6e5ec719cd8b4535967ff539d769d9c3,
title = "In vitro 3D Staphylococcus aureus abscess communities induce bone marrow cells to expand into myeloid-derived suppressor cells",
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.",
keywords = "3D in vitro model, Bone infection, Host-pathogen interaction, Myeloid-derived suppressor cell, Staphylococcal abscess community, Staphylococcus aureus",
author = "Hofstee, {Marloes I.} and Anja Heider and Sonja H{\"a}ckel and Caroline Constant and Martijn Riool and Richards, {R. Geoff} and Moriarty, {T. Fintan} and Zaat, {Sebastian A. J.}",
note = "Funding Information: Funding: This work was funded by AOTrauma as part of the clinical priority program on bone infection, project number: AR2017_05. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2021",
month = nov,
day = "1",
doi = "10.3390/pathogens10111446",
language = "English",
volume = "10",
journal = "Pathogens (Basel, Switzerland)",
issn = "2076-0817",
publisher = "MDPI AG",
number = "11",

}

RIS

TY - JOUR

T1 - In vitro 3D Staphylococcus aureus abscess communities induce bone marrow cells to expand into myeloid-derived suppressor cells

AU - Hofstee, Marloes I.

AU - Heider, Anja

AU - Häckel, Sonja

AU - Constant, Caroline

AU - Riool, Martijn

AU - Richards, R. Geoff

AU - Moriarty, T. Fintan

AU - Zaat, Sebastian A. J.

N1 - Funding Information: Funding: This work was funded by AOTrauma as part of the clinical priority program on bone infection, project number: AR2017_05. Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/11/1

Y1 - 2021/11/1

N2 - 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.

AB - 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.

KW - 3D in vitro model

KW - Bone infection

KW - Host-pathogen interaction

KW - Myeloid-derived suppressor cell

KW - Staphylococcal abscess community

KW - Staphylococcus aureus

UR - http://www.scopus.com/inward/record.url?scp=85118708724&partnerID=8YFLogxK

U2 - 10.3390/pathogens10111446

DO - 10.3390/pathogens10111446

M3 - Article

C2 - 34832602

VL - 10

JO - Pathogens (Basel, Switzerland)

JF - Pathogens (Basel, Switzerland)

SN - 2076-0817

IS - 11

M1 - 1446

ER -

ID: 20466344