Toll‐Like Receptors

Abstract

Toll‐like receptors (TLRs) are pattern recognition receptors involved in innate immunity. TLRs are expressed both intracellularly and on cell surfaces. They recognise pathogen‐associated molecular patterns on molecules associated with bacteria, fungi and viruses. TLR protein signalling culminates in the production of chemicals known as cytokines which control the inflammatory response. TLRs are expressed on a wide variety of immune and nonimmune cells and are involved in a variety of biological activities. TLR signalling is tightly regulated to prevent unnecessary inflammation. Genetic mutation of these receptors has been associated with a variety of diseases. The receptors are involved in the pathologies of conditions such as cardiovascular disease, neurodegeneration and rheumatoid arthritis. The expression of TLRs varies with cell type, age, sex and disease progression. Attempts to target TLRs pharmacologically have had some success in disease models.

Key Concepts

  • Toll‐like receptors recognise similar molecular patterns on bacteria and viruses.
  • Toll‐like receptors can relay the presence of microorganisms to intracellular protein networks.
  • Cytokine molecules are synthesised and released as a consequence of toll‐like receptor activation.
  • Toll‐like receptor activity is highly regulated in cells to prevent unnecessary inflammation.
  • Toll‐like receptor expression varies in different tissues and disease states.
  • Mutations in toll‐like receptor genes have been associated with an array of diseases.
  • Targeting toll‐like receptors with drugs may prove to be therapeutically beneficial.

Keywords: toll‐like receptors; pattern recognition receptors; inflammation; cytokines; innate immunity

Figure 1. Toll‐like receptor signalling pathways.
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Further Reading

Dowling JK and Mansell A (2016) Toll‐like receptors: the Swiss army knife of immunity and vaccine development. Clinical & Translational Immunology 5 (5): e85.

Gay NJ, Symmons MF, Gangloff M and Bryant CE (2014b) Assembly and localization of toll‐like receptor signalling complexes. Nature Reviews Immunology 14 (8): 546–558.

Hennessy C and McKernan DP (2016b) Epigenetics and innate immunity: the 'unTolld' story. Immunology & Cell Biology 94 (7): 631–639.

Iwasaki A and Medzhitov R (2015b) Control of adaptive immunity by the innate immune system. Nature Immunology 16 (4): 343–353.

Netea MG, Wijmenga C and O'Neill LA (2012b) Genetic variation in toll‐like receptors and disease susceptibility. Nature Immunology 13 (6): 535–542.

Schaefer L (2014) Complexity of danger: the diverse nature of damage‐associated molecular patterns. The Journal of Biological Chemistry 289 (51): 35237–35245.

Skevaki C, Pararas M, Kostelidou K, Tsakris A and Routsias JG (2015b) Single nucleotide polymorphisms of toll‐like receptors and susceptibility to infectious diseases. Clinical & Experimental Immunology 180 (2): 165–177.

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How to Cite close
O'Connell, Sarah, and McKernan, Declan P(Apr 2017) Toll‐Like Receptors. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0004028.pub3]