生物
TLR9型
TLR7型
细胞生物学
先天免疫系统
CpG站点
促炎细胞因子
浆细胞样树突状细胞
免疫系统
树突状细胞
CpG寡核苷酸
免疫学
炎症
基因
基因表达
Toll样受体
DNA甲基化
遗传学
作者
Amaya Iparraguirre,John W. Tobias,Scott E. Hensley,Katherine S. Masek,Lois L. Cavanagh,Michael Rendl,Christopher A. Hunter,Hildegund C. J. Ertl,Ulrich H. von Andrian,Wolfgang Weninger
摘要
Abstract There is growing evidence that plasmacytoid dendritic cells (pDC) are involved in the innate recognition of various microbes. However, the precise consequences of pathogen recognition on pDC activation and function are incompletely understood. Using a novel transgenic mouse model that facilitates the isolation of highly pure pDC populations, we found that influenza virus PR/8, a TLR7 ligand, and CpG 1826 oligonucleotide, a TLR9 ligand, induced surprisingly divergent activation programs in these cells. pDC stimulated with PR/8 produced large amounts of type I IFNs, and CpG 1826-stimulated pDC expressed higher levels of costimulatory molecules and proinflammatory cytokines and induced stronger proliferation of T cells. Transcriptome analysis uncovered the differential regulation in pDC of 178 and 1577 genes by PR/8 and CpG 1826, respectively. These differences may relate to the activation of discrete signaling pathways, as evidenced by distinct ERK1/2 and p38 MAPK phosphorylation kinetics. Finally, pDC isolated ex vivo during PR/8 infection or after i.v. CpG 1826 injection resembled their in vitro counterparts, corroborating that these cells can adopt specialized phenotypes in vivo. Thus, pDC display remarkable functional flexibility, which emphasizes their versatile functions in antimicrobial immunity and inflammatory processes.
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