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

浆细胞样树突状细胞（PDC）的激活触发大量I型干扰素（IFN-I）的分泌，使免疫细胞对微生物刺激迅速作出反应。在大多数情况下，PDC的激活依赖于核酸感应toll样受体(TLR)-7和-9的参与。这些受体被合成配体激活，如CpG DNA寡脱氧核苷酸（ODN）或鸟苷类似物，在病毒感染细胞和fc受体（FcR）介导的核酸靶向核内体。基于以往的研究结果，我们提出了PDC在抗菌免疫应答中的功能的新概念：PDC衍生的IFN-I分泌是通过fc - γ riia （CD32A）介导的内吞作用摄取细菌免疫复合物诱导的。复合物IgG分子的抗原特异性使PDC活化成为抗原特异性过程。在这种情况下，pdcs衍生的IFN-I可能在针对细菌的抗原特异性记忆反应中发挥调节作用，并可能有助于释放针对特定病原体的记忆反应。为了证明这一假设，我们设计了体外和体内实验来研究对肺炎球菌的记忆反应。本研究的重点在于分析PDC、I型干扰素和CD32在人抗肺炎球菌记忆反应中的作用。

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.