Infection of monocytes or immature dendritic cells (DCs) with an attenuated rabies virus results in DC maturation and a strong activation of the NFkappaB signaling pathway.
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.
Li
Jianwei
J
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA.
McGettigan
James P
JP
Faber
Milosz
M
Schnell
Matthias J
MJ
Dietzschold
Bernhard
B
D002454:Cell Differentiation; D003713:Dendritic Cells / Q000166:cytology* / Q000821:virology*; D006801:Humans; D009000:Monocytes / Q000821:virology*; D016328:NF-kappa B / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011820:Rabies virus / Q000472:pathogenicity*; D015398:Signal Transduction; D015854:Up-Regulation
D016328:NF-kappa B; D011506:Proteins