Toll-like receptors (TLRs)

Author: V. Dimov, M.D., Allergist/Immunologist and Assistant Professor at University of Chicago
Reviewer: S. Randhawa, M.D., Allergist/Immunologist and Assistant Professor at LSU (Shreveport) Department of Allergy and Immunology


The curved leucine-rich repeat region of toll-like receptors, represented here by TLR3. Image source: Wikipedia.


Signaling pathway of toll-like receptors. Dashed grey lines represent unknown associations. Image source: Wikipedia.

TLR 2
Two
TB and other mycobacteria

TLR4 (for LPS)

CD14

TLR 5
Five
Flagellin
Flagelated bacteria

TLR 7
Seven
SS RNA

TLR 9
Nine
Nonmethylated
Nucleotide motifs - CpG

TLR 3
Three is "Free" of MyD88

TLRs on the surface of the cells bind surface molecules: flagellin on flagellated bacteria (TLR 5), LPS (TLR 4). Our innate immune system recognizes LPS via the LPS signal transduction pathway, which has the trimolecular complex of CD14/TLR4/MD2 at the core. CD14 was the first described pattern recognition receptor (PAMP receptor).

TLRs inside the cells bind intracellular molecules - nucleic acids: TLR 3, 7, 8, 9.

TLR 3 binds to ds RNA which is never present in humans.

All TLRs except TLR 3 go through MyD88. MyD88 is an abbreviation for Myeloid differentiation primary response gene (88) (MYD88).


Pathogen Recognition Receptors, TLRs. This video is from: Janeway's Immunobiology, 7th Edition Murphy, Travers, & Walport. Source: Garland Science.

SNPs associated with atopic diseases

Filaggrin gene

Filaggrin is essential for epidermal barrier function. SNP associated with eczema and asthma.

17q12-21 gene

ORMDL3 protein defects associated with asthma.

5q22-32 gene

CD14 is a lipopolysaccharide (LPS) receptor. SNPs associated with asthma and atopy.

3p21-22 gene

CCR5 is a chemokine receptor. SNP can be protective against asthma.

Xp22 gene

TLR7 and TLR8 are recognition receptors for viral ssRNA. SNPs assciated with asthma, rhinitis, atopic dermatitis.

5q31 gene

IL-13 is a cytokine that induces IgE secretion, mucus production, and collagen synthesis (fibrosis). SNPs associated with asthma.

ADRB2 gene

ADRB2 gene encodes β2-adrenergic receptor. Argenteum (Arg) or Arg/Arg phenotype associated with decreased albuterol response compared to Gly/Gly phenotype at residue 16.

ADAM33 gene

Type 1 transmembrane protein involved in cell-to-cell interactions. SNPs associated with asthma.

Related reading:

Nickel allergy tracked to a single receptor - Toll-like receptor 4 (TLR4) http://goo.gl/PZic

Published: 07/15/2009
Updated: 08/15/2010