Rad50-CARD9 interactions link cytosolic DNA sensing to IL-1β production

Standard

Rad50-CARD9 interactions link cytosolic DNA sensing to IL-1β production. / Roth, Susanne; Rottach, Andrea; Lotz-Havla, Amelie S; Laux, Verena; Muschaweckh, Andreas; Gersting, Søren W; Muntau, Ania C; Hopfner, Karl-Peter; Jin, Lei; Vanness, Katelynd; Petrini, John H J; Drexler, Ingo; Leonhardt, Heinrich; Ruland, Jürgen.

in: NAT IMMUNOL, Jahrgang 15, Nr. 6, 01.06.2014, S. 538-45.

Publikationen: SCORING: Beitrag in Fachzeitschrift/ZeitungSCORING: ZeitschriftenaufsatzForschungBegutachtung

Harvard

Roth, S, Rottach, A, Lotz-Havla, AS, Laux, V, Muschaweckh, A, Gersting, SW, Muntau, AC, Hopfner, K-P, Jin, L, Vanness, K, Petrini, JHJ, Drexler, I, Leonhardt, H & Ruland, J 2014, 'Rad50-CARD9 interactions link cytosolic DNA sensing to IL-1β production', NAT IMMUNOL, Jg. 15, Nr. 6, S. 538-45. https://doi.org/10.1038/ni.2888

APA

Roth, S., Rottach, A., Lotz-Havla, A. S., Laux, V., Muschaweckh, A., Gersting, S. W., Muntau, A. C., Hopfner, K-P., Jin, L., Vanness, K., Petrini, J. H. J., Drexler, I., Leonhardt, H., & Ruland, J. (2014). Rad50-CARD9 interactions link cytosolic DNA sensing to IL-1β production. NAT IMMUNOL, 15(6), 538-45. https://doi.org/10.1038/ni.2888

Vancouver

Roth S, Rottach A, Lotz-Havla AS, Laux V, Muschaweckh A, Gersting SW et al. Rad50-CARD9 interactions link cytosolic DNA sensing to IL-1β production. NAT IMMUNOL. 2014 Jun 1;15(6):538-45. https://doi.org/10.1038/ni.2888

Bibtex

@article{46bf65cf340249b7a01a2051c9be63ab,
title = "Rad50-CARD9 interactions link cytosolic DNA sensing to IL-1β production",
abstract = "Double-stranded DNA (dsDNA) in the cytoplasm triggers the production of interleukin 1β (IL-1β) as an antiviral host response, and deregulation of the pathways involved can promote inflammatory disease. Here we report a direct cytosolic interaction between the DNA-damage sensor Rad50 and the innate immune system adaptor CARD9. Transfection of dendritic cells with dsDNA or infection of dendritic cells with a DNA virus induced the formation of dsDNA-Rad50-CARD9 signaling complexes for activation of the transcription factor NF-κB and the generation of pro-IL-1β. Primary cells conditionally deficient in Rad50 or lacking CARD9 consequently exhibited defective DNA-induced production of IL-1β, and Card9(-/-) mice had impaired inflammatory responses after infection with a DNA virus in vivo. Our results define a cytosolic DNA-recognition pathway for inflammation and a physical and functional connection between a conserved DNA-damage sensor and the innate immune response to pathogens.",
keywords = "Adaptor Proteins, Signal Transducing, Animals, CARD Signaling Adaptor Proteins, Cell Line, Cytosol, DNA Repair Enzymes, DNA, Viral, DNA-Binding Proteins, Dendritic Cells, Enzyme Activation, Humans, Interleukin-1beta, Membrane Proteins, Mice, Mice, Knockout, NF-kappa B, Signal Transduction, Toll-Like Receptor 4, Toll-Like Receptor 9, Vaccinia virus",
author = "Susanne Roth and Andrea Rottach and Lotz-Havla, {Amelie S} and Verena Laux and Andreas Muschaweckh and Gersting, {S{\o}ren W} and Muntau, {Ania C} and Karl-Peter Hopfner and Lei Jin and Katelynd Vanness and Petrini, {John H J} and Ingo Drexler and Heinrich Leonhardt and J{\"u}rgen Ruland",
year = "2014",
month = jun,
day = "1",
doi = "10.1038/ni.2888",
language = "English",
volume = "15",
pages = "538--45",
journal = "NAT IMMUNOL",
issn = "1529-2908",
publisher = "NATURE PUBLISHING GROUP",
number = "6",

}

RIS

TY - JOUR

T1 - Rad50-CARD9 interactions link cytosolic DNA sensing to IL-1β production

AU - Roth, Susanne

AU - Rottach, Andrea

AU - Lotz-Havla, Amelie S

AU - Laux, Verena

AU - Muschaweckh, Andreas

AU - Gersting, Søren W

AU - Muntau, Ania C

AU - Hopfner, Karl-Peter

AU - Jin, Lei

AU - Vanness, Katelynd

AU - Petrini, John H J

AU - Drexler, Ingo

AU - Leonhardt, Heinrich

AU - Ruland, Jürgen

PY - 2014/6/1

Y1 - 2014/6/1

N2 - Double-stranded DNA (dsDNA) in the cytoplasm triggers the production of interleukin 1β (IL-1β) as an antiviral host response, and deregulation of the pathways involved can promote inflammatory disease. Here we report a direct cytosolic interaction between the DNA-damage sensor Rad50 and the innate immune system adaptor CARD9. Transfection of dendritic cells with dsDNA or infection of dendritic cells with a DNA virus induced the formation of dsDNA-Rad50-CARD9 signaling complexes for activation of the transcription factor NF-κB and the generation of pro-IL-1β. Primary cells conditionally deficient in Rad50 or lacking CARD9 consequently exhibited defective DNA-induced production of IL-1β, and Card9(-/-) mice had impaired inflammatory responses after infection with a DNA virus in vivo. Our results define a cytosolic DNA-recognition pathway for inflammation and a physical and functional connection between a conserved DNA-damage sensor and the innate immune response to pathogens.

AB - Double-stranded DNA (dsDNA) in the cytoplasm triggers the production of interleukin 1β (IL-1β) as an antiviral host response, and deregulation of the pathways involved can promote inflammatory disease. Here we report a direct cytosolic interaction between the DNA-damage sensor Rad50 and the innate immune system adaptor CARD9. Transfection of dendritic cells with dsDNA or infection of dendritic cells with a DNA virus induced the formation of dsDNA-Rad50-CARD9 signaling complexes for activation of the transcription factor NF-κB and the generation of pro-IL-1β. Primary cells conditionally deficient in Rad50 or lacking CARD9 consequently exhibited defective DNA-induced production of IL-1β, and Card9(-/-) mice had impaired inflammatory responses after infection with a DNA virus in vivo. Our results define a cytosolic DNA-recognition pathway for inflammation and a physical and functional connection between a conserved DNA-damage sensor and the innate immune response to pathogens.

KW - Adaptor Proteins, Signal Transducing

KW - Animals

KW - CARD Signaling Adaptor Proteins

KW - Cell Line

KW - Cytosol

KW - DNA Repair Enzymes

KW - DNA, Viral

KW - DNA-Binding Proteins

KW - Dendritic Cells

KW - Enzyme Activation

KW - Humans

KW - Interleukin-1beta

KW - Membrane Proteins

KW - Mice

KW - Mice, Knockout

KW - NF-kappa B

KW - Signal Transduction

KW - Toll-Like Receptor 4

KW - Toll-Like Receptor 9

KW - Vaccinia virus

U2 - 10.1038/ni.2888

DO - 10.1038/ni.2888

M3 - SCORING: Journal article

C2 - 24777530

VL - 15

SP - 538

EP - 545

JO - NAT IMMUNOL

JF - NAT IMMUNOL

SN - 1529-2908

IS - 6

ER -