Journal
JOURNAL OF IMMUNOLOGY
Volume 182, Issue 11, Pages 6824-6833Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.0803001
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- BMBF Biofuture [0311896, SFB 670, SFB 704, KFO1 15, KFO 177]
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Detection of non-self RNA by TLRs within endosomes and by retinoic acid-inducible gene I (RIG-I)-like helicases in the cytosol is central to mammalian antiviral immunity. In this study, we used pathway-specific agonists and targeted delivery to address RNA immunorecognition in primary human immune cells. Within PBMC, plasmacytoid dendritic cells (pDC) and monocytes were found to be responsible for IFN-alpha production upon immunorecognition of RNA. The mechanisms of RNA recognition in pDC and monocytes were distinct. In pDC, recognition of ssRNA and dsRNA oligonucleotides was TLR7-dependent, whereas a 5' triphosphate moiety (RIG-I ligand activity) had no major contribution to IFN-a production. In monocytes, the response to RNA oligonucleotides was mediated by either TLR8 or RIG-I. TLR8 was responsible for IL-12 induction upon endosomal delivery of ssRNA oligonucleotides and RIG-I was responsible for IFN-a production upon delivery of 5' triphosphate RNA into the cytosol. In conclusion, the dissection of these pathways by selecting the appropriate structure and delivery of RNA reveals pDC as major producer of IFN-a upon TLR-mediated stimulation and monocytes as major producer of IFN-a upon RIG-I-mediated stimulation. Furthermore, our results uncover the potential of monocytes to function as major producers of H-12p70, a key Th1 cytokine classically ascribed to myeloid dendritic cells that cannot be induced by CpG oligonucleotides in the human system. The Journal of Immunology, 2009,182: 6824-6833.
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