Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8.

Details

Serval ID
serval:BIB_A94CE1BF3CCD
Type
Article: article from journal or magazin.
Collection
Publications
Title
Self-RNA-antimicrobial peptide complexes activate human dendritic cells through TLR7 and TLR8.
Journal
Journal of Experimental Medicine
Author(s)
Ganguly D., Chamilos G., Lande R., Gregorio J., Meller S., Facchinetti V., Homey B., Barrat F.J., Zal T., Gilliet M.
ISSN
1540-9538 (Electronic)
ISSN-L
0022-1007
Publication state
Published
Issued date
2009
Volume
206
Number
9
Pages
1983-1994
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
Dendritic cell (DC) responses to extracellular self-DNA and self-RNA are prevented by the endosomal seclusion of nucleic acid-recognizing Toll-like receptors (TLRs). In psoriasis, however, plasmacytoid DCs (pDCs) sense self-DNA that is transported to endosomal TLR9 upon forming a complex with the antimicrobial peptide LL37. Whether LL37 also interacts with extracellular self-RNA and how this may contribute to DC activation in psoriasis is not known. Here, we report that LL37 can bind self-RNA released by dying cells, protect it from extracellular degradation, and transport it into endosomal compartments of DCs. In pDC, self-RNA-LL37 complexes activate TLR7 and, like self-DNA-LL37 complexes, trigger the secretion of IFN-alpha without inducing maturation or the production of IL-6 and TNF-alpha. In contrast to self-DNA-LL37 complexes, self-RNA-LL37 complexes also trigger the activation of classical myeloid DCs (mDCs). This occurs through TLR8 and leads to the production of TNF-alpha and IL-6, and the differentiation of mDCs into mature DCs. We also found that self-RNA-LL37 complexes are present in psoriatic skin lesions and are associated with mature mDCs in vivo. Our results demonstrate that the cationic antimicrobial peptide LL37 converts self-RNA into a trigger of TLR7 and TLR8 in human DCs, and provide new insights into the mechanism that drives the auto-inflammatory responses in psoriasis.
Keywords
Amino Acid Sequence, Antimicrobial Cationic Peptides/genetics, Antimicrobial Cationic Peptides/immunology, Cathelicidins, Dendritic Cells/immunology, Fluorescent Antibody Technique, Humans, Immunohistochemistry, Luciferases, Macromolecular Substances/immunology, Macromolecular Substances/metabolism, Molecular Sequence Data, Psoriasis/immunology, RNA/immunology, RNA/metabolism, Toll-Like Receptor 7/immunology, Toll-Like Receptor 7/metabolism, Toll-Like Receptor 8/immunology, Toll-Like Receptor 8/metabolism
Pubmed
Web of science
Open Access
Yes
Create date
23/03/2012 11:39
Last modification date
20/08/2019 15:13
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