Cross-talk between human dendritic cell subsets influences expression of RNA sensors and inhibits picornavirus infection.
Dendritic cells (DCs) are professional antigen-presenting cells that provide a link between innate and adaptive immunity. Multiple DC subsets exist and their activation by microorganisms occurs through binding of conserved pathogen-derived structures to so-called pattern recognition receptors (PRRs). In this study we analyzed the expression of PRRs responding to viral RNA in human monocyte-derived DCs (moDCs) under steady-state or pro-inflammatory conditions. We found that mRNA and protein levels for most PRRs were increased under pro-inflammatory conditions, with the most pronounced increases in the RIG-like helicase (RLH) family. Additionally, freshly isolated human plasmacytoid DCs (pDCs) displayed significantly higher levels of TLR7, RIG-I, MDA5 and PKR as compared to myeloid DCs and moDCs. Finally, we demonstrate for the first time that cross-talk between TLR-matured or virus-stimulated pDCs and moDCs leads to a type I interferon-dependent antiviral state in moDCs. This antiviral state was characterized by enhanced RLH expression and protection against picornavirus infection. These findings might represent a novel mechanism by which pDCs can preserve the function and viability of myeloid DCs that are attracted to a site with ongoing infection, thereby optimizing the antiviral immune response.
Kramer
Matthijs
M
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Schulte
Barbara M
BM
Eleveld-Trancikova
Dagmar
D
van Hout-Kuijer
Maaike
M
Toonen
Liza W J
LW
Tel
Jurjen
J
de Vries
I Jolanda M
IJ
van Kuppeveld
Frank J M
FJ
Jansen
Bastiaan J H
BJ
Adema
Gosse J
GJ
D002450:Cell Communication; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology / Q000502:physiology; D006801:Humans; D009000:Monocytes / Q000166:cytology / Q000276:immunology; D010849:Picornaviridae / Q000472:pathogenicity; D010850:Picornaviridae Infections / Q000276:immunology*; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000378:metabolism*
D051192:Receptors, Pattern Recognition; D012313:RNA