Plasmacytoid dendritic cells are productively infected and activated through TLR-7 early after arenavirus infection.
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.
Division of Biological Sciences, University of California-San Diego, La Jolla, CA 92093, USA.
Mónica
M
Macal
Gavin M
GM
Lewis
Stefan
S
Kunz
Richard
R
Flavell
James A
JA
Harker
Elina I
EI
Zúñiga
D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology / Q000821:virology; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology*; D004195:Disease Models, Animal; D007836:Lassa virus / Q000472:pathogenicity / Q000502:physiology*; D008217:Lymphocytic choriomeningitis virus / Q000472:pathogenicity / Q000502:physiology*; D008562:Membrane Glycoproteins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011991:Receptors, Virus / Q000276:immunology / Q000378:metabolism*; D051199:Toll-Like Receptor 7 / Q000276:immunology / Q000378:metabolism*; D053585:Virus Attachment
D016207:Cytokines; D008562:Membrane Glycoproteins; D011991:Receptors, Virus; C477038:Tlr7 protein, mouse; D051199:Toll-Like Receptor 7