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

浆细胞样树突状细胞（PDC）的激活触发分泌大量的I型干扰素（IFN-I），使免疫细胞对微生物刺激迅速反应。在大多数情况下，PDC活化依赖于核酸敏感Toll样受体（TLR）-7和-9的接合。这些受体在病毒感染细胞后和Fc受体（FcR）介导的核酸靶向内体后被合成配体如CpG DNA寡脱氧核苷酸（ODN）或鸟苷类似物激活。在此基础上，我们提出了PDC在抗菌免疫应答中功能的新概念：PDC来源的IFN-Ⅰ分泌是通过FcγRIIA（CD 32A）介导的内吞作用摄取细菌免疫复合物而诱导的。复合IgG分子的抗原特异性使得PDC活化成为抗原特异性过程。在这种情况下，PDC衍生的IFN-I可能因此在对细菌的抗原特异性记忆应答中发挥调节作用，并且可能用于释放对特定病原体的记忆应答。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。研究的重点在于分析PDC、I型干扰素和CD 32在人类抗肺炎球菌记忆应答中的作用。

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.