Cytosolic sensing of extracellular self-DNA transported into monocytes by the antimicrobial peptide LL37
| Autor: | Michel Gilliet, Robert L. Modlin, Roberto Lande, Dimitrios P. Kontoyiannis, Stephan Meller, Josh Gregorio, Georgios Chamilos |
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| Rok vydání: | 2012 |
| Předmět: |
Immunology
Antimicrobial peptides Biology Real-Time Polymerase Chain Reaction Biochemistry Monocytes chemistry.chemical_compound Cytosol Cathelicidins Extracellular Humans Immunobiology Microscopy Confocal Signal transducing adaptor protein DNA Cell Biology Hematology Real-time polymerase chain reaction chemistry Interferon Type I Nucleic acid Extracellular Space Intracellular Antimicrobial Cationic Peptides |
| Zdroj: | Blood. 120:3699-3707 |
| ISSN: | 1528-0020 0006-4971 |
| Popis: | The intracellular location of nucleic acid sensors prevents recognition of extracellular self-DNA released by dying cells. However, on forming a complex with the endogenous antimicrobial peptide LL37, extracellular DNA is transported into endosomal compartments of plasmacytoid dendritic cells, leading to activation of Toll-like receptor-9 and induction of type I IFNs. Whether LL37 also transports self-DNA into nonplasmacytoid dendritic cells, leading to type I IFN production via other intracellular DNA receptors is unknown. Here we found that LL37 very efficiently transports self-DNA into monocytes, leading the production of type I IFNs in a Toll-like receptor-independent manner. This type I IFN induction was mediated by double-stranded B form DNA, regardless of its sequence, CpG content, or methylation status, and required signaling through the adaptor protein STING and TBK1 kinase, indicating the involvement of cytosolic DNA sensors. Thus, our study identifies a novel link between the antimicrobial peptides and type I IFN responses involving DNA-dependent activation of cytosolic sensors in monocytes. |
| Databáze: | OpenAIRE |
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