Toll-like Receptor

The Importance of TLRs in Innate Immunity

Toll-Like Receptors (TLRs) are a central part of the innate immune response, and are the body’s first line of defense against pathogens. They are also able to discriminate between ‘self’ and ‘non-self’ molecules which is a crucial in the prevention of autoimmune disorders.

TLRs owe their name to the Drosophila receptor Toll, which was shown to play an important role in the insect innate immune system. In mammals, there are currently 13 known homologs of Toll, of which TLRs 1-10 are found expressed in humans. TLRs 1-9 are highly conserved in human and mouse, however, TLR10 is not. TLR11 is not expressed in humans as there is a stop codon preventing generation of a full-length protein.

Most TLR signaling occurs through a TIR domain-containing adaptor, such as MyD88, TRIF, and TRAM. This results in stimulation of the NF kappa beta pathway, which in turn this regulates inflammatory cytokine production including IL-6, IL-2 and TNF-alpha, and co-stimulatory receptor expression e.g. CD86 and CD80. Together, these factors enable the body to react to infections.

Further reading:
  1. New Science Press Limited 2007, chapter 3-10; 74-45
  2. Mitchell, J.A et al (2007) J. Endo. 193;232-330
  3. Zhang, Z & Schluesener, H.J (2006) Cell. Mol. Life. Sci. 63:2901-2907
  4. Verstak, B., Hertzoa, P. & Mansell, A. (2007) Inflamm. res. 56:1-10
  5. Takeda, K & Akira, S. (2005) International Immunology 17(1):1–14

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