Titre
Cytosolic sensing of extracellular self-DNA transported into monocytes by the antimicrobial peptide LL37.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Chamilos, G.
Auteure/Auteur
Gregorio, J.
Auteure/Auteur
Meller, S.
Auteure/Auteur
Lande, R.
Auteure/Auteur
Kontoyiannis, D.P.
Auteure/Auteur
Modlin, R.L.
Auteure/Auteur
Gilliet, M.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1528-0020
Statut éditorial
Publié
Date de publication
2012
Volume
120
Numéro
18
Première page
3699
Dernière page/numéro d’article
3707
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Résumé
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.
PID Serval
serval:BIB_CEE2E851C056
PMID
Open Access
Oui
Date de création
2012-11-19T17:54:01.247Z
Date de création dans IRIS
2025-05-20T22:20:43Z