Phagocytosis of picornavirus-infected cells induces an RNA-dependent antiviral state in human dendritic cells.
Dendritic cells (DCs) play a central role in instructing antiviral immune responses. DCs, however, can become targeted by different viruses themselves. We recently demonstrated that human DCs can be productively infected with echoviruses (EVs), but not coxsackie B viruses (CVBs), both of which are RNA viruses belonging to the Enterovirus genus of the Picornaviridae family. We now show that phagocytosis of CVB-infected, type I interferon-deficient cells induces an antiviral state in human DCs. Uptake of infected cells increased the expression of the cytoplasmic RNA helicases retinoic acid-inducible gene I and melanoma differentiation-associated gene 5 as well as other interferon-stimulated genes and protected DCs against subsequent infection with EV9. These effects depended on recognition of viral RNA and could be mimicked by exposure to the synthetic double-stranded RNA analogue poly(I:C) but not other Toll-like receptor (TLR) ligands. Blocking endosomal acidification abrogated protection, suggesting a role for TLRs in the acquisition of an antiviral state in DCs. In conclusion, recognition of viral RNA rapidly induces an antiviral state in human DCs. This might provide a mechanism by which DCs protect themselves against viruses when attracted to an environment with ongoing infection.
Kramer
Matthijs
M
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Geert Grooteplein 28, 6525 GA, Nijmegen, The Netherlands.
Schulte
Barbara M
BM
Toonen
Liza W J
LW
Barral
Paola M
PM
Fisher
Paul B
PB
Lanke
Kjerstin H W
KH
Galama
Jochem M D
JM
van Kuppeveld
Frank J M
FJ
Adema
Gosse J
GJ
D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003713:Dendritic Cells / Q000276:immunology*; D006801:Humans; D018613:Microscopy, Confocal; D010587:Phagocytosis; D010849:Picornaviridae / Q000276:immunology*; D016133:Polymerase Chain Reaction; D012367:RNA, Viral / Q000378:metabolism*; D015854:Up-Regulation; D014709:Vero Cells
D012367:RNA, Viral