Assembly and localization of Toll-like receptor signalling complexes
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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TLR4 is the canonical host receptor for LPS and is required for a majority of its endotoxic and immunomodulatory effects.
“As TLR4 is the canonical host receptor for LPS and is required for a majority of its endotoxic and immunomodulatory effects20”
From Gut microbiota-derived hexa-acylated lipopolysaccharides enhance cancer immunotherapy responses (2025) · cites this paper as [20]
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Assembly of Oligomeric Death Domain Complexes during Toll Receptor Signaling*
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Two Human MYD88 Variants, S34Y and R98C, Interfere with MyD88-IRAK4-Myddosome Assembly
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Self-citation
- 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
- Licence
- www.springer.com/tdm (tdm)
- 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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