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Cell Host Microbe. 2012 Jun 14;11(6):617-30. doi: 10.1016/j.chom.2012.04.017.

Plasmacytoid dendritic cells are productively infected and activated through TLR-7 early after arenavirus infection.

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  • 1Division of Biological Sciences, University of California-San Diego, La Jolla, CA 92093, USA.

Abstract

The antiviral response is largely mediated by dendritic cells (DCs), including conventional (c) DCs that function as antigen-presenting cells, and plasmacytoid (p) DCs that produce type I interferons, making them an attractive target for viruses. We find that the Old World arenaviruses lymphocytic choriomeningitis virus clone 13 (LCMV Cl13) and Lassa virus bind pDCs to a greater extent than cDCs. Consistently, LCMV Cl13 targets pDCs early after in vivo infection of its natural murine host and establishes a productive and robust replication cycle. pDCs coproduce type I interferons and proinflammatory cytokines, with the former being induced in both infected and uninfected pDCs, demonstrating a dissociation from intrinsic virus replication. TLR7 globally mediates pDC responses, limits pDC viral load, and promotes rapid innate and adaptive immune cell activation. These early events likely help dictate the outcome of infections with arenaviruses and other DC-replicating viruses and shed light on potential therapeutic targets.

Copyright © 2012 Elsevier Inc. All rights reserved.

Comment in

PMID:
22704622
[PubMed - indexed for MEDLINE]
PMCID:
PMC3377983
Free PMC Article

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