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首页> 外文期刊>Vaccine >Infected dendritic cells are sufficient to mediate the adjuvant activity generated by Venezuelan equine encephalitis virus replicon particles.
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Infected dendritic cells are sufficient to mediate the adjuvant activity generated by Venezuelan equine encephalitis virus replicon particles.

机译:感染的树突状细胞足以介导委内瑞拉马脑炎病毒复制子颗粒产生的佐剂活性。

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Replicon particles derived from Venezuelan equine encephalitis virus (VEE) are infectious non-propagating particles which act as a safe and potent systemic, mucosal, and cellular adjuvant when delivered with antigen. VEE and VEE replicon particles (VRP) can target multiple cell types including dendritic cells (DCs). The role of these cell types in VRP adjuvant activity has not been previously evaluated, and for these studies we focused on the contribution of DCs to the response to VRP. By analysis of VRP targeting in the draining lymph node, we found that VRP induced rapid recruitment of TNF-secreting monocyte-derived inflammatory dendritic cells. VRP preferentially infected these inflammatory DCs as well as classical DCs and macrophages, with less efficient infection of other cell types. DC depletion suggested that the interaction of VRP with classical DCs was required for recruitment of inflammatory DCs, induction of high levels of many cytokines, and for stable transport of VRP to the draining lymph node. Additionally, in vitro-infected DCs enhanced antigen-specific responses by CD4 and CD8 T cells. By transfer of VRP-infected DCs into mice we showed that these DCs generated an inflammatory state in the draining lymph node similar to that achieved by VRP injection. Most importantly, VRP-infected DCs were sufficient to establish robust adjuvant activity in mice comparable to that produced by VRP injection. These findings indicate that VRP infect, recruit and activate both classical and inflammatory DCs, and those DCs become mediators of the VRP adjuvant activity.
机译:委内瑞拉马脑炎病毒(VEE)衍生的复制子颗粒是非传染性的可传播颗粒,当与抗原一起递送时可作为安全有效的全身,粘膜和细胞佐剂。 VEE和VEE复制子颗粒(VRP)可以靶向多种细胞类型,包括树突状细胞(DC)。这些细胞类型在VRP佐剂活性中的作用尚未得到评估,对于这些研究,我们集中在DC对VRP反应的贡献上。通过分析VRP靶向引流淋巴结,我们发现VRP诱导了TNF分泌单核细胞衍生的炎性树突细胞的快速募集。 VRP优先感染这些炎症性DC以及经典DC和巨噬细胞,而其他细胞类型的感染效率较低。 DC耗竭表明,VRP与经典DC的相互作用对于炎症性DC的募集,高水平的许多细胞因子的诱导以及VRP稳定转运至引流淋巴结是必需的。此外,体外感染的DC增强了CD4和CD8 T细胞的抗原特异性应答。通过将感染VRP的DC转移到小鼠中,我们发现这些DC在引流淋巴结中产生的炎症状态类似于通过VRP注射获得的炎症状态。最重要的是,受VRP感染的DC足以在小鼠中建立与VRP注射产生的佐剂活性相当的强大佐剂活性。这些发现表明,VRP感染,募集并激活经典DC和炎性DC,并且这些DC成为VRP佐剂活性的介质。

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