Table 1.
Endogenous and exogenous ligands of TLRs
| TLRs | Human | Mouse | Localization | Vascular target cells | Exogenous ligands | Origin of ligands | Endogenous ligands |
|---|---|---|---|---|---|---|---|
| TLR1 | + | + | Extracellular | Monocytes, DCs, T, B and NK cells | Soluble factors (with TLR2) | Neisseria meningitidis | Necrotic cells |
| Triacyl lipopeptides | Bacteria, mycobacteria | ApoliproteinC III | |||||
| TLR2 | + | + | Extracellular | Immune cells except T, B and NK cells | Atypical LPS | Leptospira interrogans and P. gingivalis | Ox LDL |
| Envelope glycoproteins | Virus | Serum amyloid A | |||||
| Glycoinositolphospholipids | Trypanozoma cruzi | Amyloid beta | |||||
| Glycolipids | Treponema maltophilum | Versican | |||||
| Lipoarabinomannan | Mycobacteria | ||||||
| Lipoprotein (with TLR1) | Mycobacteria, Borrelia burgdorferi | ||||||
| Lipoprotein (with TLR6) | Bacteria | ||||||
| Lipoteichoic acid | Gram-positive bacteria | ||||||
| Pam3CSK4 | Synthetic TLR2/TLR1 agonist | ||||||
| PGN | Gram-positive bacteria | ||||||
| Phenol-soluble modulin | Staphylococcus aureus | ||||||
| Phospholipomannan | Candida albicans | ||||||
| Porins | Neisseria meningitidis | ||||||
| Triacyl lipopeptides | Bacteria, mycobacteria | ||||||
| Yeast carbohydrates | |||||||
| Zymosan | Fungi | ||||||
| TLR2/TLR4 | + | + | Extracellular | Immune cells except T, B and NK cells | HSP60 | C. pneumoniae | HSP60 |
| P. gingivalis | HSP70 | ||||||
| Gp96 | |||||||
| HMGB1 | |||||||
| Hyaluronan fragment | |||||||
| Biglycan | |||||||
| TLR3 | + | + | Intracellular | Immature DCs | dsDNA | Virus | mRNA |
| TLR3/TLR9 | + | + | Intracellular | DCs | CMV | ||
| TLR4 | + | + | Extracellular | Immune cells except T, B and NK cells | LPS | Gram-negative bacteria | Lung surfactant protein-A |
| Envelope glycoproteins | Virus | Tenascin C | |||||
| Envelope proteins | MMTV | Fibrinogen | |||||
| Fusion protein | RSV | Fibronectin EDA | |||||
| HSP60 | C. pneumoniae | Heparan sulphate | |||||
| Lipoteichoic acids | Gram-positive bacteria | Beta-defensin 2 | |||||
| Mannuronic acid polymer | Aeruginosa | Minimally-modified LDL | |||||
| Protein F |
RSV Pseudomonas |
Ox LDL | |||||
| Taxol | Plant | Amyloid beta peptide | |||||
| TLR5 | + | + | Extracellular | Myelogenous cells (monocyte macrophages) | Flagellin | Bacteria | |
| TLR6 | + | + | Extracellular | Immune cells | Diacyl lipopeptides | Mycoplasma | Ox LDL |
| Group B strep heat-labile soluble factor | |||||||
| Phenol-soluble modulin | Staphylococcus aureus | ||||||
| TLR7 | + | + | Intracellular | DCs | Loxoribine and bropirimine | ||
| Various synthetic compounds including imidazoquinoline | |||||||
| TLR7/TLR8 | + | + | Intracellular | DCs | ssRNA | ||
| TLR7/TLR9 | + | + | Intracellular | DCs | Nucleic acid-containing immune complexes | ||
| TLR9 | + | + | Intracellular | DCs | HSV-2 | ||
| Hypomethylated CpG motifs in microbial DNA | |||||||
| TLR10 | + | – | Unknown | Unknown | Unknown | ||
| TLR11 | – | + | Extracellular | Nerve cells and immune cells | Uropathogenic bacteria | ||
| TLR11/TLR12 | – | + | Intracellular | Nerve cells and immune cells | Profilin | ||
| TLR13 | – | + | Intracellular | Nerve cells and immune cells | 23S rRNA |
Expression of TLRs in humans and mice and expression in and out of cells. The endogenous and exogenous ligands of TLRs, as well as the source of exogenous ligands, are listed in detail. Italics indicate that a ligand associated with atherosclerosis has been identified
DCs dendritic cells, LPS lipopolysaccharide, oxLDL oxidized low-density lipoprotein, LAM lipoarabinomannan, LTA lipoteichoic acid, PGN peptidoglycan, C. pneumoniaeChlamydia pneumonia,HSP heat-shock protein, HMGB1 high-mobility group box 1 protein, dsRNA double-stranded RNA, MMTV mouse mammary tumour virus, RSV respiratory syncytial virus, ssRNA single-stranded RNA