Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3

  title={Recognition of double-stranded RNA and activation of NF-$\kappa$B by Toll-like receptor 3},
  author={Lena Alexopoulou and Agnieszka Czopik Holt and Ruslan Medzhitov and Richard A. Flavell},
Toll-like receptors (TLRs) are a family of innate immune-recognition receptors that recognize molecular patterns associated with microbial pathogens, and induce antimicrobial immune responses. Double-stranded RNA (dsRNA) is a molecular pattern associated with viral infection, because it is produced by most viruses at some point during their replication. Here we show that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces the activation of NF-κB and the production of… 
TLR3: interferon induction by double-stranded RNA including poly(I:C).
Interferon-beta induction through toll-like receptor 3 depends on double-stranded RNA structure.
The dsRNA structure capable of inducing TLR3-mediated IFN-beta production using various synthetic RNA duplexes was analyzed and it was found that modified dsRNAs inhibited poly(I:C)-induced TLR 3-mediatedIFN- beta production by fibroblasts and DCs.
Intrinsic Cellular Defenses against Virus Infection by Antiviral Type I Interferon
These antiviral proteins play an important role of antiviral resistancy against several viral pathogens in infected cells and further activate innate immune responses.
Polyinosinic Acid Is a Ligand for Toll-like Receptor 3*
It is concluded that TLR3 is able to sense both single-stranded RNA and dsRNA, and for the first time that polyinosinic acid (poly(I))) activates B lymphocytes, dendritic cells, and macrophages and that these responses are dependent on the expression of bothTLR3 and the adaptor molecule, Toll/IL-1 receptor domain-containing adaptor inducing IFN-β (TRIF).
Human endogenous RNAs: Implications for the immunomodulation of Toll-like receptor 3.
In conclusion, TLR3 may play major physiological roles that are not in the context of viral infection and it is possible that RNA released from cells could contain enough double-stranded structures to regulate cell activation.
Activation of Innate Defense against a Paramyxovirus Is Mediated by RIG-I and TLR7 and TLR8 in a Cell-Type-Specific Manner
It is shown that activation of signal transduction and induction of cytokine expression by the paramyxovirus Sendai virus is dependent on virus replication and involves PRRs in a cell- type-dependent manner, suggesting a large degree of cell-type specificity in the mechanisms used by the host to recognize infecting viruses.
Beyond dsRNA: Toll-like receptor 3 signalling in RNA-induced immune responses.
A wide spectrum ofTLR3 ligand structures beyond dsRNA and their delivery systems provide new insights into the physiological role of TLR3 in virus- or host-derived RNA-induced immune responses.


The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5
It is reported that mammalian TLR5 recognizes bacterial flagellin from both Gram-positive and Gram-negative bacteria, and that activation of the receptor mobilizes the nuclear factor NF-κB and stimulates tumour necrosis factor-α production, and the data suggest thatTLR5, a member of the evolutionarily conserved Toll-like receptor family, has evolved to permit mammals specifically to detect flageLLated bacterial pathogens.
Immune Cell Activation by Bacterial Cpg-DNA through Myeloid Differentiation Marker 88 and Tumor Necrosis Factor Receptor–Associated Factor (Traf)6
The data suggest that CpG-DNA initiates signaling via the TLR/IL-1R pathway in APCs in a manner similar to LPS and to T helper cell–mediated CD40 ligation.
A Toll-like receptor recognizes bacterial DNA
It is shown that cellular response to CpG DNA is mediated by a Toll-like receptor, TLR9, and vertebrate immune systems appear to have evolved a specific Toll- like receptor that distinguishes bacterial DNA from self-DNA.
Cutting edge: Toll-like receptor 4 (TLR4)-deficient mice are hyporesponsive to lipopolysaccharide: evidence for TLR4 as the Lps gene product.
It is demonstrated that TLR4 is the gene product that regulates LPS response, and a single point mutation of the amino acid that is highly conserved among the IL-1/Toll receptor family is found.
Tollip, a new component of the IL-1RI pathway, links IRAK to the IL-1 receptor
It is shown that, before IL-1β treatment, Tollip is present in a complex with IRAK, and that recruitment of Tollip–IRAK complexes to the activated receptor complex occurs through association of tollip with IL- 1RAcP, and it is concluded that tollip is an important constituent of theIL-1R signalling pathway.
Potential role of PKR in double‐stranded RNA‐induced macrophage activation
Findings indicate that both NF‐κB and PKR are required for dsRNA‐induced macrophage activation; however, ds RNA‐induced NF-κB activation occurs by PKR‐independent mechanisms in macrophages.
JNK2 and IKKbeta are required for activating the innate response to viral infection.
A human homologue of the Drosophila Toll protein signals activation of adaptive immunity
The cloning and characterization of a human homologue of the Drosophila toll protein (Toll) is reported, which has been shown to induce the innate immune response in adult Dosophila.