期刊
JOURNAL OF IMMUNOLOGY
卷 190, 期 4, 页码 1591-1602出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1201222
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资金
- Deutsche Forschungsgemeinschaft [BE 384/2-1, Sonderforschungsbereich 938, FOR 876 TP1, SCHN 697/3-1, Sonderforschungsbereich 766]
- Medical Faculty of Heidelberg
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.
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