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

• Verfasst von: Parčina, Marijo [VerfasserIn]
• Verfasst von: Miranda-Garcia, Maria Auxiliadora [VerfasserIn]
• Verfasst von: Durlanik, Sibel [VerfasserIn]
• Verfasst von: Ziegler, Saskia [VerfasserIn]
• Verfasst von: Over, Benjamin [VerfasserIn]
• Verfasst von: Georg, Philipp [VerfasserIn]
• Verfasst von: Förmer, Sandra [VerfasserIn]
• Verfasst von: Ammann, Sandra [VerfasserIn]
• Verfasst von: Hilmi, Dina [VerfasserIn]
• Verfasst von: Weber, Klaus-Josef [VerfasserIn]
• Verfasst von: Schiller, Martin [VerfasserIn]
• Verfasst von: Heeg, Klaus [VerfasserIn]
• Verfasst von: Schneider-Brachert, Wulf [VerfasserIn]
• Verfasst von: Götz, Friedrich [VerfasserIn]
• Verfasst von: Bekeredjian-Ding, Isabelle [VerfasserIn]
• Titel: Pathogen-triggered activation of plasmacytoid dendritic cells induces IL-10-producing B cells in response to Staphylococcus aureus
• Verf.angabe: 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
• E-Jahr: 2013
• Jahr: February 1, 2013
• Umfang: 12 S.
• Fussnoten: Gesehen am 20.12.2021
• Titel Quelle: Enthalten in: The journal of immunology
• Ort Quelle: Bethesda, Md. : Soc., 1916
• Jahr Quelle: 2013
• Band/Heft Quelle: 190(2013), 4, Seite 1591-1602
• ISSN Quelle: 1550-6606
• DOI: doi:10.4049/jimmunol.1201222
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1782567534

Abstract

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.