Differential activation of human monocyte-derived and plasmacytoid dendritic cells by West Nile virus generated in different host cells

Maria Carlan Silva, Antonieta Guerrero-Plata, Felicia D. Gilfoy, Roberto Garofalo, Peter W. Mason

Research output: Contribution to journalArticle

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Abstract

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 WNVVero to 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 (WNV C7/10), while mDCs responded similarly to WNVVero or WNVC7/10. Moreover, the IFN-dependent chemokine IP-10 was produced in substantial amounts by pDCs in response to WNVVero but not WNV C7/10, while interleukin-8 was produced in greater amounts by mDCs infected with WNVC7/10 than in those infected with WNV Vero. 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.

Original languageEnglish (US)
Pages (from-to)13640-13648
Number of pages9
JournalJournal of Virology
Volume81
Issue number24
DOIs
StatePublished - Dec 2007

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West Nile virus
dendritic cells
monocytes
Dendritic Cells
Monocytes
interferons
cells
Interferons
chemokines
Chemokines
virus replication
Innate Immunity
Interferon Inducers
immunocompromised population
chloroquine
interferon-alpha
Viral Antigens
viral antigens
Toll-Like Receptors
Immune System Diseases

ASJC Scopus subject areas

  • Immunology

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Differential activation of human monocyte-derived and plasmacytoid dendritic cells by West Nile virus generated in different host cells. / Silva, Maria Carlan; Guerrero-Plata, Antonieta; Gilfoy, Felicia D.; Garofalo, Roberto; Mason, Peter W.

In: Journal of Virology, Vol. 81, No. 24, 12.2007, p. 13640-13648.

Research output: Contribution to journalArticle

Silva, Maria Carlan ; Guerrero-Plata, Antonieta ; Gilfoy, Felicia D. ; Garofalo, Roberto ; Mason, Peter W. / Differential activation of human monocyte-derived and plasmacytoid dendritic cells by West Nile virus generated in different host cells. In: Journal of Virology. 2007 ; Vol. 81, No. 24. pp. 13640-13648.
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