Rapid activation of spleen dendritic cell subsets following lymphocytic choriomeningitis virus infection of mice: analysis of the involvement of type 1 IFN
Rapid activation of spleen dendritic cell subsets following lymphocytic choriomeningitis virus infection of mice: analysis of the involvement of type 1 IFN
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DOI：
10.4049/jimmunol.174.4.1851
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发表时间：
2005-02-15
影响因子：
4.4
通讯作者：
Borrow, P
中科院分区：
文献类型：
--
作者：
Montoya, M;Edwards, MJ;Borrow, P
在这项研究中，我们报道了脾树突状细胞(SDC)亚群在感染一种自然的小鼠病原体--淋巴细胞性脉络膜脑膜炎病毒(LCMV)后，活化和功能的动态变化。在感染后24小时内，SDCs在体外获得了刺激初代LCMV特异性CD8(+)T细胞的能力。传统的(CD11c(高)、CD8(+)和CD4(+))SDC亚群迅速上调共刺激分子的表达，并开始产生促炎细胞因子。在体外，它们同时发生凋亡的倾向增加，而在体内，脾中常规DC的数量显著减少，到第3天下降了近2倍。相反，脾内浆细胞样树突状细胞(CD11c(Low)B220(+))数量增加，到第3天，它们几乎占到树突状细胞的40%。血浆细胞样树突状细胞经24 h pi后，1型干扰素的产生明显上调。对不能对1型干扰素应答的小鼠DC的激活和成熟的分析表明，这些细胞因子驱动感染相关的常规DC的表型激活和增强的凋亡倾向，但也表明在LCMV感染过程中存在I型干扰素非依赖的DC功能成熟途径。
In this study, we report the dynamic changes in activation and functions that occur in spleen dendritic cell (sDC) subsets following infection of mice with a natural murine pathogen, lymphocytic choriomeningitis virus (LCMV). Within 24 h postinfection (pi), sDCs acquired the ability to stimulate naive LCMV-specific CD8(+) T cells ex vivo. Conventional (CD11c(high) CD8(+) and CD4(+)) sDC subsets rapidly up-regulated expression of costimulatory molecules and began to produce proinflammatory cytokines. Their tendency to undergo apoptosis ex vivo simultaneously increased, and in vivo the number of conventional DCs in the spleen decreased markedly, dropping similar to2-fold by day 3 pi. Conversely, the number of plasmacytoid (CD11c(low)B220(+)) DCs in the spleen increased, so that they constituted almost 40% of sDCs by day 3 pi. Type 1 IFN production was up-regulated in plasmacytoid DCs by 24 h pi. Analysis of DC activation and maturation in mice unable to respond to type 1 IFNs implicated these cytokines in driving infection-associated phenotypic activation of conventional DCs and their enhanced tendency to undergo apoptosis, but also indicated the existence of type I IFN-independent pathways for the functional maturation of DCs during LCMV infection.