Cytosolic sensing of extracellular self-DNA transported into monocytes by the antimicrobial peptide LL37

Author:

Chamilos Georgios12,Gregorio Josh1,Meller Stephan1,Lande Roberto34,Kontoyiannis Dimitrios P.2,Modlin Robert L.5,Gilliet Michel13

Affiliation:

1. Departments of Immunology and

2. Infectious Diseases, The University of Texas MD Anderson Cancer Center, Houston, TX;

3. Department of Dermatology, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland;

4. Department of Infectious, Parasitic and Immunomediated Diseases, Istituto Superiore di Sanità, Rome, Italy; and

5. Division of Dermatology, UCLA David Geffen School of Medicine, Los Angeles, CA

Abstract

AbstractThe 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

Reference39 articles.

1. Type I interferons (alpha/beta) in immunity and autpimmunity.;Theofilopoulos;Annu Rev Immunol,2005

2. Type I interferons in host defense.;Stetson;Immunity,2006

3. Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice.;Santini;J Exp Med,2000

4. Type I IFNs enhance the terminal differentiation of dendritic cells.;Luft;J Immunol,1998

5. Intracellular DNA recognition.;Hornung;Nat Rev Immunol,2010

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