RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III–transcribed RNA intermediate

Ablasser, Andrea; Bauernfeind, Franz; Hartmann, Gunther; Latz, Eicke; Fitzgerald, Katherine A.; Hornung, Veit

doi:10.1038/ni.1779

Cited by 752 publications

(739 citation statements)

References 56 publications

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“…Indeed, the struc-npg ture of RIG-I bound to short dsRNA products has recently been solved [88,89]. RIG-I has also recently been implicated in the recognition of DNA viruses by binding short dsRNAs generated by RNA polIII [90]. However, it has been shown that RIG-I can directly recognize ssRNA genomes containing 5′ triphosphates, and suggested that for negative stranded RNA viruses, this may be the relevant PAMP [91].…”

Section: Pattern Recognition Receptorsmentioning

confidence: 99%

NF-κB in immunobiology

2011

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NF-κB was first discovered and characterized 25 years ago as a key regulator of inducible gene expression in the immune system. Thus, it is not surprising that the clearest biological role of NF-κB is in the development and function of the immune system. Both innate and adaptive immune responses as well as the development and maintenance of the cells and tissues that comprise the immune system are, at multiple steps, under the control of the NF-κB family of transcription factors. Although this is a well-studied area of NF-κB research, new and significant findings continue to accumulate. This review will focus on these areas of recent progress while also providing a broad overview of the roles of NF-κB in mammalian immunobiology.

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Section: Pattern Recognition Receptorsmentioning

confidence: 99%

NF-κB in immunobiology

2011

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“…Most DNA-sensing PRR (DAI, IFI16, AIM2, DHX9) signaling pathways converge in the activation and nuclear translocation of NF-κB to drive the expression of proinflammatory transcriptional targets. To investigate the role of this pathway, we used a plasmid encoding the IκBα-super repressor (IκBα-SR), which functions similarly to endogenous IκBα in its ability to bind and protein 16 (IFI16), 12 leucine rich repeat flightless-interacting protein (LRRFIP1), 13 probable ATP-dependent RNA helicase DDX41 14 and RNA polymerase III, 15 which transcribes dsDNA into double stranded RNA leading to RIG-I activation. However, which of these DNA-sensing signaling pathways promotes the maturation of APCs after DNA electroporation leading to the generation of CTL responses is not fully understood, especially for intradermal vaccination.…”

Section: Nf-κb Activation During Intradermal Dna Vaccination Is Essenmentioning

confidence: 99%

NF-κB activation during intradermal DNA vaccination is essential for eliciting tumor protective antigen-specific CTL responses

Ligtenberg

Rojas-Colonelli

Kiessling

et al. 2013

Human Vaccines & Immunotherapeutics

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“…25 RNA variants can be recognised by the retinoic acid-induced gene-like helicase family that includes the 2 0 -5 0 -oligoadenylate synthetase (Oas) subfamily. 26,27 We first searched the array data for genes associated with these families of PRR molecules and their downstream pathways, some of which overlap.…”

Section: Go Biological Process Term Mappingmentioning

confidence: 99%

Molecular signature of the immune and tissue response to non-coding plasmid DNA in skeletal muscle after electrotransfer

et al. 2011

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Electrotransfer of plasmid DNA in skeletal muscle is a common non-viral delivery method for both therapeutic genes and DNA vaccines. Yet, despite the similar approaches, an immune response is detrimental in gene therapy, but desirable for vaccines. However, the full nature of the immune and tissue responses to nucleic acids and electrotransfer in skeletal muscle has not been addressed. Here we used microarray analysis, fluorescence-activated cell sorting and quantitative polymerase chain reaction to obtain the molecular and cellular signature of the tissue and immune response to electrotransfer of saline and non-coding plasmid DNA. Saline electrotransfer resulted in limited infiltration and induction of a moderate damage --repair gene expression pattern not involving innate immune activation. However, plasmid electrotransfer augmented expression of the same genes in addition to inducing a strong innate immune response associated with pro-inflammatory infiltration. In particular, the inflammasome, Toll-like receptor 9 and other pattern recognition receptors able to respond to cytoplasmic DNA were upregulated. Several key differences in the nature of the inflammatory infiltrate and the kinetics of gene expression were also identified when comparing electrotransfer of conventional and CpG-free plasmids. Our data provide insights into the mechanisms of DNA detection and response in muscle that has relevance for non-viral gene therapy and DNA vaccination.

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RIG-I-dependent sensing of poly(dA:dT) through the induction of an RNA polymerase III–transcribed RNA intermediate

Cited by 752 publications

References 56 publications

NF-κB in immunobiology

NF-κB in immunobiology

NF-κB activation during intradermal DNA vaccination is essential for eliciting tumor protective antigen-specific CTL responses

Molecular signature of the immune and tissue response to non-coding plasmid DNA in skeletal muscle after electrotransfer

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