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: Matthijs Kramer, Barbara M Schulte, Dagmar Eleveld-Trancikova, Maaike van Hout-Kuijer, Liza W J Toonen, Jurjen Tel, I Jolanda M de Vries, Frank J M van Kuppeveld, Bastiaan J H Jansen, Gosse J Adema
• Journal: Journal of innate immunity (J Innate Immun) Vol. 2 Issue 4 Pg. 360-70 ( 2010) ISSN: 1662-8128 [Electronic] Switzerland
• PMID: 20375561 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2010 S. Karger AG, Basel.

Chemical References

• Receptors, Pattern Recognition
• RNA

Topics

• Cell Communication
• Cells, Cultured
• Dendritic Cells (cytology, immunology, physiology)
• Humans
• Monocytes (cytology, immunology)
• Picornaviridae (pathogenicity)
• Picornaviridae Infections (immunology)
• RNA (genetics, metabolism)
• Receptors, Pattern Recognition (genetics, metabolism)