Kassim Sadik H, Rajasagi Naveen K, Zhao Xiangyi, Chervenak Robert, Jennings Stephen R
Department of Microbiology and Immunology, Louisiana State University Health Sciences Center, Shreveport 71130, USA.
J Virol. 2006 Apr;80(8):3985-93. doi: 10.1128/JVI.80.8.3985-3993.2006.
The precise role of each of the seven individual CD11c+ dendritic cell subsets (DCs) identified to date in the response to viral infections is not known. DCs serve as critical links between the innate and adaptive immune responses against many pathogens, including herpes simplex virus type 1 (HSV-1). The role of DCs as mediators of resistance to HSV-1 infection was investigated using CD11c-diphtheria toxin (DT) receptor-green fluorescent protein transgenic mice, in which DCs can be transiently depleted in vivo by treatment with low doses of DT. We show that ablation of DCs led to enhanced susceptibility to HSV-1 infection in the highly resistant C57BL/6 mouse strain. Specifically, we showed that the depletion of DCs led to increased viral spread into the nervous system, resulting in an increased rate of morbidity and mortality. Furthermore, we showed that ablation of DCs impaired the optimal activation of NK cells and CD4+ and CD8+ T cells in response to HSV-1. These data demonstrated that DCs were essential not only in the optimal activation of the acquired T-cell response to HSV-1 but also that DCs were crucial for innate resistance to HSV-1 infection.
迄今为止确定的七种个体CD11c⁺树突状细胞亚群（DCs）在对病毒感染的反应中各自的确切作用尚不清楚。DCs是针对包括单纯疱疹病毒1型（HSV-1）在内的许多病原体的固有免疫反应和适应性免疫反应之间的关键纽带。使用CD11c-白喉毒素（DT）受体-绿色荧光蛋白转基因小鼠研究了DCs作为抵抗HSV-1感染的介质的作用，在这种小鼠中，低剂量DT处理可使DCs在体内短暂耗竭。我们发现，在高度抗性的C57BL/6小鼠品系中，DCs的消融导致对HSV-1感染的易感性增强。具体而言，我们发现DCs的耗竭导致病毒向神经系统扩散增加，从而导致发病率和死亡率上升。此外，我们发现DCs的消融损害了NK细胞以及CD4⁺ 和CD8⁺ T细胞对HSV-1反应的最佳激活。这些数据表明，DCs不仅对于获得性T细胞对HSV-1反应的最佳激活至关重要，而且对于抵抗HSV-1感染的固有免疫也至关重要。
