title: Staphylococcus aureus-induced plasmacytoid dendritic cell activation is based on an IgG-mediated memory response.
abstract: 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-alpha 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 alpha-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.
authors.affiliation: Department of Medical Microbiology and Hygiene, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: Marijo
authors.initials: M
authors.lastname: Parcina
authors.forename: Constanze
authors.initials: C
authors.lastname: Wendt
authors.forename: Friedrich
authors.initials: F
authors.lastname: Goetz
authors.forename: Rainer
authors.initials: R
authors.lastname: Zawatzky
authors.forename: Ulrich
authors.initials: U
authors.lastname: Zähringer
authors.forename: Klaus
authors.initials: K
authors.lastname: Heeg
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bekeredjian-Ding