Steel Christina D, Hahto Suzanne M, Ciavarra Richard P
Department of Microbiology and Molecular Cell Biology, Eastern Virginia Medical School, 700 W Olney Road, Norfolk, VA 23501, USA.
Virology. 2009 Apr 25;387(1):117-26. doi: 10.1016/j.virol.2009.01.032. Epub 2009 Mar 4.
Intranasal application of vesicular stomatitis virus (VSV) causes acute infection of the central nervous system (CNS). However, VSV encephalitis is not invariably fatal, suggesting that the CNS may contain a professional antigen-presenting cell (APC) capable of inducing or propagating a protective antiviral immune response. To examine this possibility, we first characterized the cellular elements that infiltrate the brain as well as the activation status of resident microglia in the brains of normal and transgenic mice acutely ablated of peripheral dendritic cells (DCs) in vivo. VSV encephalitis was characterized by a pronounced infiltrate of myeloid cells (CD45(high)CD11b(+)) and CD8(+) T cells containing a subset that was specific for the immunodominant VSV nuclear protein epitope. This T cell response correlated temporally with a rapid and sustained upregulation of MHC class I expression on microglia, whereas class II expression was markedly delayed. Ablation of peripheral DCs profoundly inhibited the inflammatory response as well as infiltration of virus-specific CD8(+) T cells. Unexpectedly, the VSV-induced interferon-gamma (IFN-gamma) response in the CNS remained intact in DC-deficient mice. Thus, both the inflammatory and certain components of the adaptive primary antiviral immune response in the CNS are dependent on peripheral DCs in vivo.
经鼻内接种水泡性口炎病毒（VSV）可导致中枢神经系统（CNS）急性感染。然而，VSV脑炎并非总是致命的，这表明中枢神经系统可能含有一种能够诱导或传播保护性抗病毒免疫反应的专职抗原呈递细胞（APC）。为了检验这种可能性，我们首先对正常小鼠和体内外周树突状细胞（DC）被急性清除的转基因小鼠大脑中浸润的细胞成分以及驻留小胶质细胞的激活状态进行了表征。VSV脑炎的特征是髓样细胞（CD45(高)CD11b(+)）和CD8(+) T细胞明显浸润，其中包含一个对免疫显性VSV核蛋白表位具有特异性的亚群。这种T细胞反应在时间上与小胶质细胞上MHC I类表达的快速持续上调相关，而II类表达则明显延迟。外周DC的清除显著抑制了炎症反应以及病毒特异性CD8(+) T细胞的浸润。出乎意料的是，在缺乏DC的小鼠中，CNS中VSV诱导的干扰素-γ（IFN-γ）反应仍然完好无损。因此，中枢神经系统中炎症反应和适应性原发性抗病毒免疫反应的某些成分在体内均依赖于外周DC。
