Cited by 832Immune Response and InflammationInflammasome and immune disordersNF-κB Signaling Pathways

Assembly and localization of Toll-like receptor signalling complexes

Gay, Nicholas J., Symmons, Martyn F., Gangloff, Monique, Bryant, Clare E.·2014·Nature Reviews Immunology

Abstract

Signal transduction by the Toll-like receptors (TLRs) is central to host defence against many pathogenic microorganisms and also underlies a large burden of human disease. Thus, the mechanisms and regulation of signalling by TLRs are of considerable interest. In this Review, we discuss the molecular basis for the recognition of pathogen-associated molecular patterns, the nature of the protein complexes that mediate signalling, and the way in which signals are regulated and integrated at the level of allosteric assembly, post-translational modification and subcellular trafficking of the components of the signalling complexes. These fundamental molecular mechanisms determine whether the signalling output leads to a protective immune response or to serious pathologies such as sepsis. A detailed understanding of these processes at the molecular level provides a rational framework for the development of new drugs that can specifically target pathological rather than protective signalling in inflammatory and autoimmune disease.

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Crossref · 10.1038/nri3713

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Authors
Gay, N. J., Symmons, M. F., Gangloff, M., & Bryant, C. E.
Affiliations
University of Cambridge (GB)
Corresponding author
Gay, Nicholas J.
Venue
Nature Reviews Immunology
Published
2014-07-25
Volume
14
Issue
8
Pages
546-558
ISSN
  • 1474-1733 (ISSN-L)
  • 1474-1741
OpenAlex
W2038554653
Cited by
832
References
113
Citations by year
2026: 28 · 2025: 53 · 2024: 73 · 2023: 66 · 2022: 75 · 2021: 104 · 2020: 93 · 2019: 54 · 2018: 77 · 2017: 81 · 2016: 77 · 2015: 48 · 2014: 2
FWCI
6.63
Type
journal article
Language
en
Open access
closed
Locations
  • Nature reviews. Immunology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Wellcome Trust (100321, 100321/Z/12/Z, WT100321/z/12/Z, WT081744/Z/06/Z)
  • Biotechnology and Biological Sciences Research Council (BB/K006436/1)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
Keywords
Toll-like receptors, Toll-like receptor signaling, adaptor proteins, pathogen-associated molecular patterns, post-translational modification, intracellular trafficking, signal transduction, innate immunity, sepsis, inflammatory diseases, autoimmune disease, therapeutic target
MeSH terms
Animals, Drosophila melanogaster, Humans, Immunity, Innate, Protein Processing, Post-Translational, Signal Transduction, Protein Transport, Drosophila Proteins, Receptors, Pattern Recognition, Toll-Like Receptors, Myeloid Differentiation Factor 88

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