Toll-Like Receptor Signaling Pathways
Click on one of the Toll-like receptors shown in the Explore Pathways box below to see the pathogen-associated molecules recognized by each receptor & the intracellular signaling pathways that are activated as a result.
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IFN-alpha
IFN-alpha 1
IFN-alpha 2
IFN-alpha 4
IFN-alpha A
IFN-alpha B2
IFN-alpha C
IFN-alpha D
IFN-alpha F
IFN-alpha H2
IFN-alpha I
IFN-alpha J1
IFN-alpha K
IFN-alpha WA
IFN-alpha 11
IFN-alpha 13
IFN-beta
IFN-kappa
IFN-omega
IL-28A/IFN-lambda 2
IL-28B/IFN-lambda 3
IL-28A/B (IFN-lambda 2/3)
IL-29/IFN-lambda 1
IL-29/IL-28B (IFN-lambda 1/3)
Limitin/IFN-zeta
| Select Ligand(s) for TLR1/TLR2 | Source |
|---|---|
| Triacyl lipopeptides | Bacteria |
| Select Ligand(s) for TLR2 | Source |
|---|---|
| Lipoproteins | Multiple pathogens |
| Peptidoglycan (PGN) | Bacteria |
| Porins | Bacteria |
| Zymosan | Fungi |
| beta-Glycan | Fungi |
| GPI-mucin | Protozoa |
| Envelope glycoproteins | Viruses |
| Select Ligand(s) for TLR3 | Source |
|---|---|
| Double-stranded RNA | Viruses |
| Poly (I:C) | Synthetic analog of ds-RNA |
| Select Ligand(s) for TLR4 | Source |
|---|---|
| Lipopolysaccharides (LPS) | Bacteria |
| Glycoinositolphospholipids | Protozoa |
| Envelope glycoproteins | Viruses |
| Select Ligand(s) for TLR5 | Source |
|---|---|
| Flagellin | Bacteria |
| Select Ligand(s) for TLR2/TLR6 | Source |
|---|---|
| Diacyl lipopeptides | Bacteria |
| Lipoteichoic acid (LTA) | Bacteria |
| Select Ligand(s) for TLR7 | Source |
|---|---|
| Single-stranded RNA | Viruses |
| Select Ligand(s) for TLR8 | Source |
|---|---|
| Single-stranded RNA | Viruses |
| Select Ligand(s) for TLR9 | Source |
|---|---|
| Bacteria | |
| Unmethylated CpG DNA | Protozoa |
| Viruses |
| Select Ligand(s) for TLR10 | Source |
|---|---|
| Unknown | Unknown |
Overview of Toll-like Receptors
Toll-like receptors (TLRs) are a family of transmembrane pattern recognition receptors that detect invading pathogens and initiate the innate and adaptive immune response. Different TLRs are expressed on distinct subsets of immune and non-immune cell types, including macrophages, dendritic cells, B cells, T cells, fibroblasts, and epithelial cells. TLRs are activated following recognition of specific conserved pathogen-associated molecular patterns (PAMPs) present in microbial proteins, nucleic acids, lipids, or carbohydrates. Recognition of these molecules by TLRs triggers signal transduction cascades that ultimately induce the expression of pro-inflammatory cytokines and Type I or Type III interferons or IFN-inducible genes. Expression of these cytokines promotes the recruitment of additional leukocytes to the infection site, which together act to eliminate the pathogenic microbes and infected cells. Ten human TLRs have been identified that are expressed either on the cell surface (TLR1, 2, 4, 5, 6, and 10) or in intracellular compartments (TLR3, 7, 8, and 9). Each TLR has a variable number of ligand-sensing leucine-rich repeats at its N-terminal end and a cytoplasmic Toll/IL-1 receptor (TIR) domain. This domain is also conserved in proteins belonging to the IL-1 receptor family and a number of intracellular adaptor proteins that mediate TLR signaling, including MyD88, TRAM, TRIF, and TIRAP. Polymorphisms in TLRs or in specific TLR signaling molecules are associated with increased susceptibility to microbial infections and autoimmune disorders.
To learn more, please visit our Toll-Like Receptors Research Area.
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