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:	Marloes I. Hofstee, Anja Heider, Sonja Häckel, Caroline Constant, Martijn Riool, R. Geoff Richards, T. Fintan Moriarty, Sebastian A. J. Zaat
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>Staphylococcus aureus</i> staphylococcal abscess community myeloid-derived suppressor cell 3D in vitro model bone infection host-pathogen interaction Medicine R
Acceso en línea:	https://doaj.org/article/9c002aee20ab48efa46220de3f3e0464
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spelling	oai:doaj.org-article:9c002aee20ab48efa46220de3f3e04642021-11-25T18:38:19ZIn Vitro 3D <i>Staphylococcus aureus</i> Abscess Communities Induce Bone Marrow Cells to Expand into Myeloid-Derived Suppressor Cells10.3390/pathogens101114462076-0817https://doaj.org/article/9c002aee20ab48efa46220de3f3e04642021-11-01T00:00:00Zhttps://www.mdpi.com/2076-0817/10/11/1446https://doaj.org/toc/2076-0817<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.Marloes I. HofsteeAnja HeiderSonja HäckelCaroline ConstantMartijn RioolR. Geoff RichardsT. Fintan MoriartySebastian A. J. ZaatMDPI AGarticle<i>Staphylococcus aureus</i>staphylococcal abscess communitymyeloid-derived suppressor cell3D in vitro modelbone infectionhost-pathogen interactionMedicineRENPathogens, Vol 10, Iss 1446, p 1446 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>Staphylococcus aureus</i> staphylococcal abscess community myeloid-derived suppressor cell 3D in vitro model bone infection host-pathogen interaction Medicine R
spellingShingle	<i>Staphylococcus aureus</i> staphylococcal abscess community myeloid-derived suppressor cell 3D in vitro model bone infection host-pathogen interaction Medicine R Marloes I. Hofstee Anja Heider Sonja Häckel Caroline Constant Martijn Riool R. Geoff Richards T. Fintan Moriarty Sebastian A. J. Zaat In Vitro 3D <i>Staphylococcus aureus</i> Abscess Communities Induce Bone Marrow Cells to Expand into Myeloid-Derived Suppressor Cells
description	<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.
format	article
author	Marloes I. Hofstee Anja Heider Sonja Häckel Caroline Constant Martijn Riool R. Geoff Richards T. Fintan Moriarty Sebastian A. J. Zaat
author_facet	Marloes I. Hofstee Anja Heider Sonja Häckel Caroline Constant Martijn Riool R. Geoff Richards T. Fintan Moriarty Sebastian A. J. Zaat
author_sort	Marloes I. Hofstee
title	In Vitro 3D <i>Staphylococcus aureus</i> Abscess Communities Induce Bone Marrow Cells to Expand into Myeloid-Derived Suppressor Cells
title_short	In Vitro 3D <i>Staphylococcus aureus</i> Abscess Communities Induce Bone Marrow Cells to Expand into Myeloid-Derived Suppressor Cells
title_full	In Vitro 3D <i>Staphylococcus aureus</i> Abscess Communities Induce Bone Marrow Cells to Expand into Myeloid-Derived Suppressor Cells
title_fullStr	In Vitro 3D <i>Staphylococcus aureus</i> Abscess Communities Induce Bone Marrow Cells to Expand into Myeloid-Derived Suppressor Cells
title_full_unstemmed	In Vitro 3D <i>Staphylococcus aureus</i> Abscess Communities Induce Bone Marrow Cells to Expand into Myeloid-Derived Suppressor Cells
title_sort	in vitro 3d <i>staphylococcus aureus</i> abscess communities induce bone marrow cells to expand into myeloid-derived suppressor cells
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/9c002aee20ab48efa46220de3f3e0464
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In Vitro 3D <i>Staphylococcus aureus</i> Abscess Communities Induce Bone Marrow Cells to Expand into Myeloid-Derived Suppressor Cells

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