Vaccinia virus impairs directional migration and chemokine receptor switch of human dendritic cells
Vaccinia virus impairs directional migration and chemokine receptor switch of human dendritic cells
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DOI：
10.1002/eji.200636230
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发表时间：
2007-04-01
影响因子：
5.4
通讯作者：
Jenne, Lars
中科院分区：
文献类型：
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作者：
Humrich, Jens Y.;Thumann, Peter;Jenne, Lars
诱导抗病毒免疫应答的关键事件是树突状细胞（DC）向感染部位和次级淋巴器官的协调的、表型依赖性的迁移。在这里，我们表明，牛痘病毒（VV）株Western Reserve（WR）和改良病毒安卡拉（MVA）抑制定向迁移成熟的DC向淋巴样趋化因子CCL 19和CXCL 12，而不影响表面表达的相应的趋化因子受体或损害无定向细胞运动。相反，VV感染导致细胞外信号调节激酶-1缺乏和细胞内钙动员紊乱，表明病毒干扰表面趋化因子受体下游的信号传导事件。在未成熟DC中，除了抑制趋化因子诱导的受感染DC的迁移外，用两种VV菌株感染增加了未感染的旁观者DC上炎性趋化因子受体CCR 1和CXCR 1的表达，这取决于IFN-α的活性。虽然功能，这些趋化因子受体是抵抗脂多糖诱导的下调。此外，VV感染和未感染的旁观者DC在激活后不能上调淋巴趋化因子受体CCR 7，共同指向经历趋化因子受体转换的残疾。这项研究表明VV靶向多个功能水平的专职抗原呈递细胞的定向迁移，揭示了免疫逃逸的有效病毒策略。
A crucial event for the induction of an anti-viral immune response is the coordinated, phenotype-dependent migration of dendritic cells (DC to sites of infection and secondary lymphoid organs. Here we show that the vaccinia virus (VV) strains Western Reserve (WR) and modified virus Ankara (MVA) inhibit directional migration of mature DC toward the lymphoid chemokines CCL19 and CXCL12 without affecting surface expression of the respective chemokine receptors or impairing undirected cellular locomotion. Instead, infection with VV results in a deficiency of extracellular signal-regulated kinase-1 and a disturbance of intracellular calcium mobilization, indicating a viral interference with signaling events downstream of the surface chemokine receptors. In immature DC, apart from inhibiting chemokine-induced migration of infected DC, infection with both VV strains increases expression of the inflammatory chemokine receptors CCR1 and CXCR1 on non-infected bystander DC, which depends on the activity of IFN-alpha. Although functional, these chemokine receptors are resistant to lipopolysaccharide-induced down-regulation. In addition, VV-infected and noninfected bystander DC fail to up-regulate the lymphoid chemokine receptor CCR7 upon activation, together pointing to a disability to undergo the chemokine receptor switch. This study shows that VV targets directional migration of professional antigen-presenting cells at multiple functional levels, revealing a potent viral strategy of immune escape.