Viral entry route determines how human plasmacytoid dendritic cells produce type I interferons.
Although plasmacytoid dendritic cells (pDCs) represent a rare immune cell type, they are the most important source of type I interferons (IFNs) upon viral infection. Phagocytosed RNA viruses and RNA virus-infected cells are detected by pDCs with the endosomal pattern recognition receptor (PRR) toll-like receptor 7 (TLR7). We showed that replication of the yellow fever live vaccine YF-17D in human pDCs and pDC-like cell lines stimulated type I IFN production through RIG-I (retinoic acid-inducible gene I), a member of the RIG-I-like receptor (RLR) family of cytosolic PRRs. Thus, human pDCs sense replicative viral RNA. In contrast, direct contact between pDCs and YF-17D-infected cells stimulated a TLR7-dependent, viral replication-independent production of type I IFN. We also showed that the RLR pathway was dampened by the activities of interleukin-1 receptor-associated kinases 1 and 4 (IRAK1 and IRAK4), which are downstream effectors of the TLR7 pathway, suggesting that both kinases play opposing roles downstream of specific PRRs. Together, these data suggest that a virus can stimulate either TLR or RLR signaling in the same cell, depending on how its nucleic acid content is delivered.
Department of Virology, Viral Genomics and Vaccination, UMR CNRS 3569, Pasteur Institute, 75015 Paris, France.
Daniela
D
Bruni
Department of Virology, Viral Genomics and Vaccination, UMR CNRS 3569, Pasteur Institute, 75015 Paris, France.
Maxime
M
Chazal
Department of Virology, Viral Genomics and Vaccination, UMR CNRS 3569, Pasteur Institute, 75015 Paris, France.
Laura
L
Sinigaglia
Department of Virology, Virus and Immunity, UMR CNRS 3569, Pasteur Institute, 75015 Paris, France.
Lise
L
Chauveau
Department of Virology, Virus and Immunity, UMR CNRS 3569, Pasteur Institute, 75015 Paris, France.
Olivier
O
Schwartz
Department of Infection and Epidemiology, Pasteur Institute, 75015 Paris, France. UMR U1187, Processus Infectieux en Milieu Insulaire Tropicale (I2T team), Cyclotron Réunion Océan Indien, 97490 Saint-Denis, La Reunion, France.
Philippe
P
Desprès
Department of Virology, Viral Genomics and Vaccination, UMR CNRS 3569, Pasteur Institute, 75015 Paris, France. jouvenet@pasteur.fr.
Nolwenn
N
Jouvenet
D000328:Adult; D000818:Animals; D002522:Chlorocebus aethiops; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D003713:Dendritic Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D005260:Female; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D008297:Male; D010950:Plasma Cells / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D012367:RNA, Viral / Q000096:biosynthesis*; D011971:Receptors, Immunologic; D051199:Toll-Like Receptor 7 / Q000378:metabolism; D014709:Vero Cells; D053586:Virus Internalization; D014779:Virus Replication / Q000502:physiology*; D015005:Yellow fever virus / Q000502:physiology*
D007370:Interferon Type I; D012367:RNA, Viral; D011971:Receptors, Immunologic; C495348:TLR7 protein, human; D051199:Toll-Like Receptor 7; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases