Bréhin Anne-Claire, Mouriès Juliette, Frenkiel Marie-Pascale, Dadaglio Gilles, Desprès Philippe, Lafon Monique, Couderc Thérèse
Neuro-Immunologie Virale, Institut Pasteur, Paris, France.
J Immunol. 2008 May 15;180(10):6760-7. doi: 10.4049/jimmunol.180.10.6760.
West Nile virus (WNV) is an emerging neurotropic flavivirus. We investigated the dynamics of immune cell recruitment in peripheral tissues and in the CNS during WNV encephalitis in an immunocompetent mouse model. In the periphery, immune cell expansion can successfully limit viremia and lymphoid tissue infection. However, viral clearance in the periphery is too late to prevent viral invasion of the CNS. In the CNS, innate immune cells, including microglia/macrophages, NK cells, and plasmacytoid dendritic cells, greatly expand as the virus invades the brain, whereas B and T cells are recruited after viral invasion, and fail to control the spread of the virus. Thus, the onset of WNV encephalitis was correlated both with CNS viral infection and with a large local increase of innate immune cells. Interestingly, we identify a new immune cell type: CD19(+)B220(-) BST-2(+), which we name G8-ICs. These cells appear during peripheral infection and enter the CNS. G8-ICs express high levels of MHC class II, stain for viral Ag, and are localized in the paracortical zone of lymph nodes, strongly suggesting they are previously unidentified APCs that appear in response to viral infection.
西尼罗河病毒(WNV)是一种新出现的嗜神经性黄病毒。我们在具有免疫活性的小鼠模型中研究了WNV脑炎期间外周组织和中枢神经系统中免疫细胞募集的动态变化。在外周,免疫细胞的扩增能够成功限制病毒血症和淋巴组织感染。然而,外周的病毒清除为时已晚,无法阻止病毒侵入中枢神经系统。在中枢神经系统中,随着病毒侵入大脑,包括小胶质细胞/巨噬细胞、自然杀伤细胞和浆细胞样树突状细胞在内的固有免疫细胞大量扩增,而B细胞和T细胞在病毒侵入后才被募集,且无法控制病毒的传播。因此,WNV脑炎的发病既与中枢神经系统病毒感染有关,也与固有免疫细胞在局部大量增加有关。有趣的是,我们鉴定出一种新的免疫细胞类型:CD19(+)B220(-)BST-2(+),我们将其命名为G8-ICs。这些细胞在外周感染期间出现并进入中枢神经系统。G8-ICs高表达MHC II类分子,可被病毒抗原染色,定位于淋巴结的副皮质区,强烈提示它们是先前未被识别的抗原呈递细胞,在病毒感染时出现。