Collaboration of Toll-like and RIG-I-like receptors in human dendritic cells: tRIGgering antiviral innate immune responses

Dendritic cells (DCs) represent a functionally diverse and flexible population of rare cells with the unique capability of binding, internalizing and detecting various microorganisms and their components. However, the response of DCs to innocuous or pathogenic microbes is highly dependent on the type of microbe-associated molecular patterns (MAMPs) recognized by pattern recognition receptors (PRRs) that interact with phylogenetically conserved and functionally indispensable microbial targets that involve both self and foreign structures such as lipids, carbohydrates, proteins, and nucleic acids. Recently, special attention has been drawn to nucleic acid receptors that are able to evoke robust innate immune responses mediated by type I interferons and inflammatory cytokine production against intracellular pathogens. Both conventional and plasmacytoid dendritic cells (cDCs and pDCs) express specific nucleic acid recognizing receptors, such as members of the membrane Toll-like receptor (TLR) and the cytosolic RIG-I-like receptor (RLR) families. TLR3, TLR7/TLR8 and TLR9 are localized in the endosomal membrane and are specialized for the recognition of viral double-stranded RNA, single-stranded RNA, and nonmethylated DNA, respectively whereas RLRs (RIG-I, MDA5, and LGP2) are cytosolic proteins that sense various viral RNA species. In this review we discuss the significance of detecting the genomic content of viruses by DC subsets capable of linking innate and adaptive immunity, and several viral evasion mechanisms that may allow us to better understand these responses. A particular attention is paid to the possible collaboration of TLR and RLR sensors in anti-viral protection.