The history of Toll-like receptors — redefining innate immunity

  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},
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… 

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.

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.

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.

Novel drugs targeting Toll-like receptors for antiviral therapy.

Recent advances in TLR biology are explored with a focus on novel drugs that target TLRs (agonists and antagonists) for antiviral therapy.

TLRs/NLRs: Shaping the landscape of host immunity

The critical roles of TLRs and NLRs in the regulation of host immune-effector functions such as cytokine production, phagosome-lysosome fusion, inflammasome activation, autophagy, antigen presentation, and B and T cell immune responses that are known to be essential for mounting a protective immune response against the pathogens are discussed.



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.

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.