Plasmacytoid Dendritic Cell-mediated Regulation of the Memory Response to Pneumococci

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Activation of plasmacytoid dendritic cells (PDC) triggers the secretion of high amounts of type I interferons (IFN-I) that prime immune cells to rapidly respond to microbial stimuli. In most cases PDC activation is dependent on the engagement of the nucleic acid-sensing Toll-like receptors (TLR)-7 and -9. These receptors are activated by synthetic ligands such as CpG DNA oligodesoxynucleotides (ODN) or guanosine analogues, upon viral infection of the cell and upon Fc-receptor (FcR)-mediated targeting of nucleic acids to the endosome. Based on previous results we propose a new concept for the function of PDC in the antibacterial immune response: PDC-derived IFN-I secretion is induced via uptake of bacterial immune complexes by FcγRIIA (CD32A)-mediated endocytosis. Antigenspecificity of the complexed IgG molecule makes PDC activation an antigen-specific process. In this context PDC-derived IFN-I may therefore exert a regulatory role in the antigen-specific memory response to bacteria and could possibly serve to unleash the memory response to a specific pathogen. To prove this hypothesis we have designed in vitro and in vivo experiments to study the memory response to pneumococci. The focus of the study lies on the analysis of the role of PDC, type I interferons and of CD32 in the human anti-pneumococcal memory response.