The history of Toll-like receptors — redefining innate immunity

@article{ONeill2013TheHO,
  title={The history of Toll-like receptors — redefining innate immunity},
  author={Luke A. J. O’Neill and Douglas T. Golenbock and Andrew G. Bowie},
  journal={Nature Reviews Immunology},
  year={2013},
  volume={13},
  pages={453-460}
}
The discovery of Toll-like receptors (TLRs) was an important event for immunology research and was recognized as such with the awarding of the 2011 Nobel Prize in Physiology or Medicine to Jules Hoffmann and Bruce Beutler, who, together with Ralph Steinman, the third winner of the 2011 Nobel Prize and the person who discovered the dendritic cell, were pioneers in the field of innate immunity. TLRs have a central role in immunity — in this Timeline article, we describe the landmark findings that… 
View on Nature
tara.tcd.ie
1,388 Citations
Highly Influential Citations
90
Background Citations
563
Methods Citations
23
Results Citations
3

1,388 Citations

Of Flies and Men—The Discovery of TLRs

The discoveries leading up to the publications of Beutler and Hoffmann are collected, taking a close look at how early advances in both developmental biology and immunology converged into the research awarded with the Nobel Prize.

Anti-tumor Activity of Toll-Like Receptor 7 Agonists

The anti-tumor activity and mechanism of TLR7 agonists that are frequently applied in preclinical and clinical investigations are reviewed, and mainly focused on small synthetic molecules, including imiquimod, resiquIMod, gardiquimmod, and 852A, etc.

Innate Immune Receptors.

The different families of PRRs, their signalling pathways, cross-regulation and their roles in immunosurveillance are introduced and the structure and function of NLRs are discussed with particular focus on the non-inflammasome NLRs.

TLR4 in Atherogenesis: Paying the Toll for Antimicrobial Defense.

  • J. Fuster
  • Biology
    Journal of the American College of Cardiology
  • 2018

Microbial-Derived Toll-like Receptor Agonism in Cancer Treatment and Progression

The aim of this review is to draw attention to the effects of TLR stimulation in cancer, the activation of various TLRs by microbes in different types of tumors, and, finally, the role of TLRs in anti-cancer immunity and tumor rejection.

PRR Function of Innate Immune Receptors in Recognition of Bacteria or Bacterial Ligands.

Recognition of a bacterial attack is the first and the most important step in clearing the bacteria from the body of the host. Towards this, the host innate immune system employs pattern recognition…

Toll-Like Receptors as a Therapeutic Target in the Era of Immunotherapies

A perspective on TLR-based therapeutics is offered that sheds light on their usefulness and on combination therapies and highlights various therapeutics that are in the discovery phase or in clinical trials.

Modulation of Toll-like receptor signaling in innate immunity by natural products.

Natural Products with Toll-Like Receptor 4 Antagonist Activity

Molecules obtained by natural sources have been discovered to exert an anti-inflammatory action by targeting TLR4 activation pathways, and this review focuses onTLR4 antagonists obtained from bacteria, cyanobacteria, and plants.

TLRs Go Linear - On the Ubiquitin Edge.

...

References

SHOWING 1-10 OF 126 REFERENCES

The roles of TLRs, RLRs and NLRs in pathogen recognition.

Recent insights into pathogen sensing by PRRs are summarized and specific signaling pathways that lead to expression of genes that tailor immune responses to particular microbes are summarized.

TLR11 Activation of Dendritic Cells by a Protozoan Profilin-Like Protein

A profilin-like molecule from the protozoan parasite Toxoplasma gondii is identified that generates a potent interleukin-12 (IL-12) response in murine DCs that is dependent on myeloid differentiation factor 88 and is the first chemically defined ligand for this TLR.

Control of B-cell responses by Toll-like receptors

It is found that, in addition to CD4+ T-cell help, generation of T-dependent antigen-specific antibody responses requires activation of TLRs in B cells.

Pattern recognition receptors TLR4 and CD14 mediate response to respiratory syncytial virus

A common receptor activation pathway can initiate innate immune responses to both bacterial and viral pathogens.

Therapeutic Targeting of Toll-Like Receptors for Infectious and Inflammatory Diseases and Cancer

Recent advances in the understanding of signaling pathways activated by TLRs, structural insights into TLRs bound to their ligands and antagonists, and approaches to inhibit TLRs are providing possible means by which to interfere with TLRs clinically.

The repertoire for pattern recognition of pathogens by the innate immune system is defined by cooperation between toll-like receptors.

The data suggest that TLRs sample the contents of the phagosome independent of the nature of the contents, and can establish a combinatorial repertoire to discriminate among the large number of pathogen-associated molecular patterns found in nature.

Genetic variation in Toll-like receptors and disease susceptibility

This work has demonstrated complex interaction between genetic variation in TLRs and environmental factors that explains the differences in the effect of TLR polymorphisms on susceptibility to infection and autoimmune disease in various populations.

Recognition of profilin by Toll-like receptor 12 is critical for host resistance to Toxoplasma gondii.

Structures of the toll-like receptor family and its ligand complexes.

Discrimination of bacterial lipoproteins by Toll-like receptor 6.

Results show that TLR6 recognizes MALP-2 cooperatively with TLR2, and appears to discriminate between the N-terminal lipoylated structures of MALp-2 and lipopeptides derived from other bacteria.
...