Parcina, Marijo and Miranda-Garcia, Maria Auxiliadora and Durlanik, Sibel and Ziegler, Saskia and Over, Benjamin and Georg, Philipp and Foermer, Sandra and Ammann, Sandra and Hilmi, Dina and Weber, Klaus-Josef and Schiller, Martin and Heeg, Klaus and Schneider-Brachert, Wulf and Goetz, Friedrich and Bekeredjian-Ding, Isabelle (2013) Pathogen-Triggered Activation of Plasmacytoid Dendritic Cells Induces IL-10-Producing B Cells in Response to Staphylococcus aureus. JOURNAL OF IMMUNOLOGY, 190 (4). pp. 1591-1602. ISSN 0022-1767, 1550-6606
Full text not available from this repository. (Request a copy)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 V(H)3(+) 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/scid(Prkdc)/gamma c(-/-) 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. The Journal of Immunology, 2013, 190: 1591-1602.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | INTERFERON-ALPHA-BETA; NECROSIS-FACTOR-ALPHA; HUMAN-LYMPHOCYTES; I INTERFERON; SUBCLASS DISTRIBUTION; T-CELLS; RIG-I; PROTEIN; EXPRESSION; VIRUS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Apr 2020 09:48 |
| Last Modified: | 24 Apr 2020 09:48 |
| URI: | https://pred.uni-regensburg.de/id/eprint/17141 |
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