Differential activation of human monocyte-derived and plasmacytoid dendritic cells by West Nile virus generated in different host cells
| Autor: | Maria Carlan Silva, Roberto P. Garofalo, Peter W. Mason, Felicia D. Gilfoy, Antonieta Guerrero-Plata |
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| Rok vydání: | 2007 |
| Předmět: |
Chemokine
viruses Immunology Virus Replication Microbiology Virus Monocytes Cell Line Species Specificity Aedes Virology Chlorocebus aethiops medicine Animals Humans Vero Cells Cells Cultured Innate immune system biology Monocyte virus diseases Interferon-alpha Cell Differentiation Dendritic cell Dendritic Cells biology.organism_classification Virus-Cell Interactions Flavivirus medicine.anatomical_structure Viral replication Insect Science biology.protein Vero cell Chemokines West Nile virus |
| Zdroj: | Journal of virology. 81(24) |
| ISSN: | 1098-5514 |
| Popis: | Dendritic cells (DCs) play a central role in innate immunity and antiviral responses. In this study, we investigated the production of alpha interferon (IFN-α) and inducible chemokines by human monocyte-derived dendritic cells (mDCs) and plasmacytoid dendritic cells (pDCs) infected with West Nile virus (WNV), an emergent pathogen whose infection can lead to severe cases of encephalitis in the elderly, children, and immunocompromised individuals. Our experiments demonstrated that WNV grown in mammalian cells (WNVVero) was a potent inducer of IFN-α secretion in pDCs and, to a lesser degree, in mDCs. The ability of WNVVeroto induce IFN-α in pDCs did not require viral replication and was prevented by the treatment of cells with bafilomycin A1 and chloroquine, suggesting that it was dependent on endosomal Toll-like receptor recognition. On the other hand, IFN-α production in mDCs required viral replication and was associated with the nuclear translocation of IRF3 and viral antigen expression. Strikingly, pDCs failed to produce IFN-α when stimulated with WNV grown in mosquito cells (WNVC7/10), while mDCs responded similarly to WNVVeroor WNVC7/10. Moreover, the IFN-dependent chemokine IP-10 was produced in substantial amounts by pDCs in response to WNVVerobut not WNVC7/10, while interleukin-8 was produced in greater amounts by mDCs infected with WNVC7/10than in those infected with WNVVero. These findings suggest that cell-specific mechanisms of WNV recognition leading to the production of type I IFN and inflammatory chemokines by DCs may contribute to both the innate immune response and disease pathogenesis in human infections. |
| Databáze: | OpenAIRE |
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