Species-Specific Recognition of Single-Stranded RNA via Toll-like Receptor 7 and 8

  title={Species-Specific Recognition of Single-Stranded RNA via Toll-like Receptor 7 and 8},
  author={Florian Heil and Hiroaki Hemmi and Hubertus Hochrein and Franziska Ampenberger and Carsten J. Kirschning and Shizuo Akira and Grayson B. Lipford and Hermann Wagner and Stefan Bauer},
  pages={1526 - 1529}
Double-stranded ribonucleic acid (dsRNA) serves as a danger signal associated with viral infection and leads to stimulation of innate immune cells. In contrast, the immunostimulatory potential of single-stranded RNA (ssRNA) is poorly understood and innate immune receptors for ssRNA are unknown. We report that guanosine (G)- and uridine (U)-rich ssRNA oligonucleotides derived from human immunodeficiency virus–1 (HIV-1) stimulate dendritic cells (DC) and macrophages to secrete interferon-α and… 

Toll-like receptor 8 senses degradation products of single-stranded RNA

It is demonstrated that TLR8 is a sensor for both uridine and a short oligonucleotide derived from RNA, and both binding sites were essential for activation ofTLR8 by ssRNA.

Phosphorylation of RNA Molecules ¢ Highly Dependent on the Size and the 5 Monocyte-Derived Dendritic Cells Are Innate Immune Responses in Human

The data suggest that human monocyte-derived dendritic cells (moDCs) are extremely sensitive in recognizing foreign RNA, and the responses depend on RNA size, form (ssRNA versus dsRNA), and the size of the RNA molecule.

Development of TLR7/8 small RNA antagonists.

  • M. Sioud
  • Biology
    Methods in molecular biology
  • 2010
This chapter describes the characterization of immunosuppressive RNA oligonucleotides carrying 2'-modified uridines, which may have utility as inhibitors of pathogenic inflammatory reactions mediated by TLR activation.

Synthetic double-stranded RNA oligonucleotides are immunostimulatory for chicken spleen cells

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).

Innate Immune Responses in Human Monocyte-Derived Dendritic Cells Are Highly Dependent on the Size and the 5′ Phosphorylation of RNA Molecules

The data suggest that human moDCs are extremely sensitive in recognizing foreign RNA, and the responses depend on RNA size, form (ssRNA versus dsRNA), and the level of 5′ phosphorylation, whereas ssRNA-induced responses were less dependent on the size of the RNA molecule.

Inosine-Mediated Modulation of RNA Sensing by Toll-Like Receptor 7 (TLR7) and TLR8

It is demonstrated for the first time that inosine incorporation into immunostimulatory ssRNA can potentiate TLR7/8 activation and suggest a novel function of A-to-I RNA editing, which is to facilitate TLR 7/8 sensing of phagocytosed viral RNA.



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

It is shown that mammalian TLR3 recognizes dsRNA, and that activation of the receptor induces the activation of NF-κB and the production of type I interferons (IFNs).

Toll-like Receptor 9–mediated Recognition of Herpes Simplex Virus-2 by Plasmacytoid Dendritic Cells

A novel mechanism whereby the genomic DNA of a virus can engage TLR9 and result in the secretion of IFN-α by pDCs is demonstrated.

Human TLR9 confers responsiveness to bacterial DNA via species-specific CpG motif recognition

It is shown that human TLR9 expression in human immune cells correlates with responsiveness to bacterial deoxycytidylate-phosphate-deoxyguanylate (CpG)-DNA, and data suggest that hTLR9 conveys CpG-DNA responsiveness to human cells by directly engaging immunostimulating Cpg-DNA.

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.

Molecular basis for the immunostimulatory activity of guanine nucleoside analogs: Activation of Toll-like receptor 7

  • Jongdae LeeT. Chuang H. Cottam
  • Biology, Chemistry
    Proceedings of the National Academy of Sciences of the United States of America
  • 2003
Evidence is presented that guanosine analogs activate immune cells via TLR7 by a pathway that requires endosomal maturation, and the B cell-stimulating and antiviral activities of the guanosin analogs may be explained by theirTLR7-activating capacity.

Toll-like receptors.

The innate immune system in drosophila and mammals senses the invasion of microorganisms using the family of Toll receptors, stimulation of which initiates a range of host defense mechanisms and there is evidence for additional pathways that mediate TLR ligand-specific biological responses.

Chromatin–IgG complexes activate B cells by dual engagement of IgM and Toll-like receptors

It is shown that effective activation of RF+ B cells is mediated by IgG2a–chromatin immune complexes and requires the synergistic engagement of the antigen receptor and a member of the MyD88-dependent Toll-like receptor (TLR) family.

The Toll‐like receptor 7 (TLR7)‐specific stimulus loxoribine uncovers a strong relationship within the TLR7, 8 and 9 subfamily

It is concluded that TLR7, 8 and 9 form a functional subgroup within the TLR family that recognizes pathogen‐associated molecular patterns in endosomal/lysosomal compartments.

Three novel mammalian toll-like receptors: gene structure, expression, and evolution.

A single present-day representative of the Toll-like proteins in Drosophila has striking cytoplasmic domain homology to mammalian Tlrs within the cluster that embraces TLRs 1, 2, 4, and 6, which would suggest that an ancestral (pre-vertebrate) Tlr may have adopted a pro-inflammatory function 500 million years ago.