Li Jianwei, McGettigan James P, Faber Milosz, Schnell Matthias J, Dietzschold Bernhard
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA.
Vaccine. 2008 Jan 17;26(3):419-26. doi: 10.1016/j.vaccine.2007.10.072. Epub 2007 Nov 29.
To assess the potential role of dendritic cells (DCs) or monocytes in the development of a protective immune response, we infected human immature DCs or monocytes with a live rabies virus (RV) vaccine strain (SPBNGAS-GAS) and a pathogenic RV (DOG4). Both cell types were infected with SPBNGAS-GAS and DOG4 and both RVs were similarly potent in inducing maturation of immature DCs or monocytes. However, in contrast to DOG4, SPBNGAS-GAS induced very high levels of IFN-alpha1 mRNA in monocytes and DCs. Furthermore, at least 26 other genes related to the NFkappaB signaling pathway were strongly upregulated in SPBNGAS-GAS-infected DCs, but only somewhat increased in DOG4-infected cells. Thus, the extent of upregulation of NFkappaB pathway-related genes in DCs infected with the live RV vaccine strain might explain the strong protective activity of SPBNGAS-GAS.
为评估树突状细胞(DCs)或单核细胞在保护性免疫反应发展中的潜在作用,我们用一种活狂犬病病毒(RV)疫苗株(SPBNGAS-GAS)和一种致病性RV(DOG4)感染人未成熟DCs或单核细胞。两种细胞类型均被SPBNGAS-GAS和DOG4感染,且两种RV在诱导未成熟DCs或单核细胞成熟方面同样有效。然而,与DOG4不同,SPBNGAS-GAS在单核细胞和DCs中诱导出非常高水平的IFN-α1 mRNA。此外,至少26个与NFκB信号通路相关的其他基因在被SPBNGAS-GAS感染的DCs中强烈上调,但在被DOG4感染的细胞中仅略有增加。因此,被活RV疫苗株感染的DCs中NFκB通路相关基因上调的程度可能解释了SPBNGAS-GAS的强大保护活性。