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* Department of Medical Microbiology and Hygiene, University Hospital Heidelberg, Heidelberg, Germany;
Microbial Genetics, University Tuebingen, Tuebingen, Germany;
Deutsches Krebsforschungszentrum, Heidelberg, Germany; and
Division of Immunochemistry, Research Center Borstel, Borstel, Germany
Type I IFNs represent a major antimicrobial defense mechanism due to their property of enhancing immune responses by priming both innate and adaptive immune cells. Plasmacytoid dendritic cells (pDC) are the major source of type I IFN in the human body and represent innate immune cells involved in first-line defense against invading pathogens. Although pDC activation has been extensively studied upon stimulation with synthetic TLR ligands, viruses, and intracellular bacteria, there is only scarce information on extracellular bacteria. In this study we show that the triggering of human pDC-derived IFN-
secretion by Staphylococcus aureus is independent of TLR2 and specific for coagulase-positive staphylococci. Specificity of the pDC response to S. aureus is independent of the bacterial virulence factors protein A and -toxin but is mediated by Ag-specific IgG and CD32. S. aureus-induced pDC activation can be blocked by inhibitory DNA oligonucleotides and chloroquine, suggesting that engagement of TLR7/9 by bacterial nucleic acids after CD32-mediated uptake of these compounds may play a central role in this process. Altogether, we propose that in marked contrast to nonselective TLR2-dependent activation of most innate immune cells, pDC activation by S. aureus represents an Ag-specific memory response since it requires the presence of class-switched immunoglobulins.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 I.B.-D. is supported by a research fellowship from the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and the Olympia Morata program of the University of Heidelberg. This study is part of the doctoral thesis of M.P. The study was further supported by the Deutsche Forschungsgemeinschaft (DFG) Sonderforschungsbereiche (SFB) 405 "Immune Tolerance and Its Disturbances" to K.H., DFG Priority Program "Innate Immunity" SPP 1110 to U.Z., and DFG SFB 766 "Bacterial Cell Envelope: Structure, Function and Infection Interface" to F.G.
2 Address correspondence and reprint requests to Dr. Isabelle Bekeredjian-Ding, Department of Medical Microbiology and Hygiene, University Hospital Heidelberg, Im Neuenheimer Feld 324, 1.OG, D-69120 Heidelberg, Germany. E-mail address: isabelle.bekeredjian-ding{at}med.uni-heidelberg.de
3 Abbreviations used in this paper: pDC, plasmacytoid dendritic cells; LP, lipopeptides; NDV, Newcastle disease virus; ODN, oligodesoxynucleotide; SpA, staphylococcal protein A; WT, wild type.
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