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首页> 外文期刊>Journal of Leukocyte Biology: An Official Publication of the Reticuloendothelial Society >Two distinct activation states of plasmacytoid dendritic cells induced by influenza virus and CpG 1826 oligonucleotide.
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Two distinct activation states of plasmacytoid dendritic cells induced by influenza virus and CpG 1826 oligonucleotide.

机译：流感病毒和CpG 1826寡核苷酸诱导的浆细胞样树突状细胞的两个不同的激活状态。

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摘要

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.
机译：越来越多的证据表明，浆细胞样树突状细胞（pDC）参与了各种微生物的先天识别。但是，尚不完全了解病原体识别对pDC激活和功能的确切影响。使用一种新型的转基因小鼠模型来促进高纯度pDC群体的分离，我们发现流感病毒PR / 8（一种TLR7配体）和CpG 1826寡核苷酸（一种TLR9配体）在这些细胞中诱导了令人惊讶的趋异激活程序。 PR / 8刺激的pDC产生大量I型IFN，CpG 1826刺激的pDC表达更高水平的共刺激分子和促炎细胞因子，并诱导更强的T细胞增殖。转录组分析揭示了PR / 8和CpG 1826分别对178和1577基因在pDC中的差异调节。这些差异可能与离散信号通路的激活有关，如不同的ERK1 / 2和p38 MAPK磷酸化动力学所证明。最后，pDC在PR / 8感染期间或静脉内分离后离体分离。 CpG 1826注射类似于它们的体外对应物，证实了这些细胞可以在体内采用特殊的表型。因此，pDC显示出显着的功能灵活性，这强调了它们在抗菌素免疫和炎症过程中的多功能性。

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