title: Pathogen-triggered activation of plasmacytoid dendritic cells induces IL-10-producing B cells in response to Staphylococcus aureus.
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)/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.
authors: Department of Infectious Diseases, Medical Microbiology, and Hygiene, University Hospital Heidelberg, D-69120 Heidelberg, Germany.
authors: Marijo
authors: M
authors: Parcina
authors: María Auxiliadora
authors: MA
authors: Miranda-Garcia
authors: Sibel
authors: S
authors: Durlanik
authors: Saskia
authors: S
authors: Ziegler
authors: Benjamin
authors: B
authors: Over
authors: Philipp
authors: P
authors: Georg
authors: Sandra
authors: S
authors: Foermer
authors: Sandra
authors: S
authors: Ammann
authors: Dina
authors: D
authors: Hilmi
authors: Klaus-Josef
authors: KJ
authors: Weber
authors: Martin
authors: M
authors: Schiller
authors: Klaus
authors: K
authors: Heeg
authors: Wulf
authors: W
authors: Schneider-Brachert
authors: Friedrich
authors: F
authors: Götz
authors: Isabelle
authors: I
authors: Bekeredjian-Ding
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D002454:Cell Differentiation / Q000276:immunology; D002460:Cell Line; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D057809:HEK293 Cells; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D016753:Interleukin-10 / Q000096:biosynthesis*; D051379:Mice; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D008822:Mice, Transgenic; D013203:Staphylococcal Infections / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D013205:Staphylococcal Protein A / Q000494:pharmacology*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D007074:Immunoglobulin G; D013205:Staphylococcal Protein A; D016753:Interleukin-10