title: Cross-talk between human dendritic cell subsets influences expression of RNA sensors and inhibits picornavirus infection.
abstract: 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.
authors.affiliation: Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Kramer
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Schulte
authors.forename: Dagmar
authors.initials: D
authors.lastname: Eleveld-Trancikova
authors.forename: Maaike
authors.initials: M
authors.lastname: van Hout-Kuijer
authors.forename: Liza W J
authors.initials: LW
authors.lastname: Toonen
authors.forename: Jurjen
authors.initials: J
authors.lastname: Tel
authors.forename: I Jolanda M
authors.initials: IJ
authors.lastname: de Vries
authors.forename: Frank J M
authors.initials: FJ
authors.lastname: van Kuppeveld
authors.forename: Bastiaan J H
authors.initials: BJ
authors.lastname: Jansen
authors.forename: Gosse J
authors.initials: GJ
authors.lastname: Adema
mesh_terms: 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*
chemical_list: D051192:Receptors, Pattern Recognition; D012313:RNA