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Pathogen-triggered activation of plasmacytoid dendritic cells induces IL-10-producing B cells in response to Staphylococcus aureus

Induction of polyclonal B cell activation is a phenomenon observed in many types of infection, but its immunological relevance is unclear. In this study we show that staphylococcal protein A induces T cell-independent human B cell proliferation by enabling uptake of TLR-stimulating nucleic acids via...

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Main Authors: Parčina, Marijo (Author) , Miranda-Garcia, Maria Auxiliadora (Author) , Durlanik, Sibel (Author) , Ziegler, Saskia (Author) , Over, Benjamin (Author) , Georg, Philipp (Author) , Förmer, Sandra (Author) , Ammann, Sandra (Author) , Hilmi, Dina (Author) , Weber, Klaus-Josef (Author) , Schiller, Martin (Author) , Heeg, Klaus (Author) , Schneider-Brachert, Wulf (Author) , Götz, Friedrich (Author) , Bekeredjian-Ding, Isabelle (Author)
Format: Article (Journal)
Language:English
Published: February 1, 2013
In: The journal of immunology
Year: 2013, Volume: 190, Issue: 4, Pages: 1591-1602
ISSN:1550-6606
DOI:10.4049/jimmunol.1201222
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.4049/jimmunol.1201222
Verlag, lizenzpflichtig, Volltext: https://www.jimmunol.org/content/190/4/1591
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Author Notes:Marijo Parcina, María Auxiliadora Miranda-Garcia, Sibel Durlanik, Saskia Ziegler, Benjamin Over, Philipp Georg, Sandra Foermer, Sandra Ammann, Dina Hilmi, Klaus-Josef Weber, Martin Schiller, Klaus Heeg, Wulf Schneider-Brachert, Friedrich Götz, and Isabelle Bekeredjian-Ding
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Summary:Induction of polyclonal B cell activation is a phenomenon observed in many types of infection, but its immunological relevance is unclear. In this study we show that staphylococcal protein A induces T cell-independent human B cell proliferation by enabling uptake of TLR-stimulating nucleic acids via the VH3+ BCR. We further demonstrate that Staphylococcus aureus strains with high surface protein A expression concomitantly trigger activation of human plasmacytoid dendritic cells (pDC). Sensitivity to chloroquine, cathepsin B inhibition, and a G-rich inhibitory oligodeoxynucleotide supports the involvement of TLR9 in this context. We then identify pDC as essential cellular mediators of B cell proliferation and Ig production in response to surface protein A-bearing S. aureus. The in vivo relevancy of these findings is confirmed in a human PBMC Nod/scidPrkdc/γc−/− mouse model. Finally, we demonstrate that co-operation of pDC and B cells enhances B cell-derived IL-10 production, a cytokine associated with immunosuppression and induction of IgG4, an isotype frequently dominating the IgG response to S. aureus. IL-10 release is partially dependent on TLR2-active lipoproteins, a hallmark of the Staphylococcus species. Collectively, our data suggest that S. aureus exploits pDC and TLR to establish B cell-mediated immune tolerance.
Item Description:Gesehen am 20.12.2021
Physical Description:Online Resource
ISSN:1550-6606
DOI:10.4049/jimmunol.1201222

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