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J. Virol. doi:10.1128/JVI.00857-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

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

Department of Pathology, University of Texas Medical Branch (UTMB), Galveston, TX 77555, USA; Department of Pediatrics, UTMB, Galveston, TX 77555; Sealy Center for Vaccine Development UTMB, Galveston, TX 77555; Department of Microbiology & Immunology, UTMB, Galveston, TX 77555

^* To whom correspondence should be addressed. Email: pwmason{at}utmb.edu.

	Abstract

Dendritic cells (DCs) play a central role in innate immunity and antiviral responses. In this study we investigated the production of interferon (IFN) 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 elderly, children and immunocompromised individuals. Our experiments demonstrated that WNV grown in mammalian cells (WNV^Vero) was a potent inducer of IFN secretion in pDCs and to a lesser degree in mDCs. The ability of WNV^Vero to induce IFN in pDCs did not require viral replication and was prevented by treatment of the cells with chloroquine, suggesting that it was dependent on endosomal toll-like receptor (TLR) recognition. On the other hand, IFN production in mDCs required viral replication and was associated with nuclear translocation of IRF3 and viral antigen expression. Strikingly, pDCs failed to produce IFN when stimulated with WNV grown in mosquito cells (WNV^C7/10), while mDCs responded similarly to WNV^Vero or WNV^C7/10. Moreover, the IFN-dependent chemokine IP-10 was produced in substantial amounts by pDCs in response to WNV^Vero but not WNV^C7/10, while IL-8 was produced in greater amounts by mDCs infected with WNV^C7/10 than WNV^Vero. These findings suggest that cell-specific mechanisms of WNV recognition leading to production of IFN type I and inflammatory chemokines by DCs may contribute to both innate immune response and disease pathogenesis in human infections.

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