Toll-Like Receptor Signaling Pathways

Click on one of the Toll-like receptors 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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TLR1/TLR2
TLR1/TLR2
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CD14
CD14
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TIRAP
TIRAP
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MyD88
MyD88
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TLR2/TLR6
TLR2/TLR6
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CD14
CD14
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CD36
CD36
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TIRAP
TIRAP
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MyD88
MyD88
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IRAK4
IRAK4
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IRAK1/2
IRAK1/2
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TRAF-6
TRAF-6
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TAB1/2
TAB1/2
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TAK1
TAK1
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TRAF-6
TRAF-6
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IKK
IKK
I kappa B
I kappa B
I kappa B
I kappa B
Proteasome
Proteasome
NF-kappa B
NF-kappa B
NF-kappa B
NF-kappa B
MKK
MKK
p38
p38
JNK
JNK
AP-1
AP-1
IL-1 beta,
IL-1 beta,
TNF-alpha,
TNF-alpha,
IL-6,
IL-6,
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IL-8,
IL-8,
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IL-18
IL-18
Proinflammatory Cytokines:
Proinflammatory Cytokines:
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TLR3
TLR3
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TRIF
TRIF
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TRAF-3
TRAF-3
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TANK
TANK
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TBK1
TBK1
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IKK epsilon
IKK epsilon
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IRF3
IRF3
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IRF3 Homodimer
IRF3 Homodimer
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IRF7
IRF7
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IRF7 Homodimer
IRF7 Homodimer
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IRF3 or IRF7
IRF3 or IRF7
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RIP1
RIP1
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TAB1/2
TAB1/2
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TAK1
TAK1
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TRAF-6
TRAF-6
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IKK
IKK
I kappa B
I kappa B
I kappa B
I kappa B
Proteasome
Proteasome
NF-kappa B
NF-kappa B
NF-kappa B
NF-kappa B
MKK
MKK
p38
p38
JNK
JNK
AP-1
AP-1
TLR4
TLR4
MD-2
MD-2
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CD14
CD14
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TRAM
TRAM
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TRIF
TRIF
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TIRAP
TIRAP
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MyD88
MyD88
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TRAF-3
TRAF-3
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TANK
TANK
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TBK1
TBK1
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IKK epsilon
IKK epsilon
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IRF3
IRF3
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IRF3 Homodimer
IRF3 Homodimer
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IRF3
IRF3
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RIP1
RIP1
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TLR5
TLR5
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MyD88
MyD88
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TLR7
TLR7
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MyD88
MyD88
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TRAF-3
TRAF-3
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IRF7
IRF7
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IRF7 Homodimer
IRF7 Homodimer
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IRF7
IRF7
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TLR8
TLR8
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MyD88
MyD88
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TLR9
TLR9
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MyD88
MyD88
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TLR10
TLR10
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MyD88
MyD88
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Type I or Type III IFN or IFN-inducible genes
Type I or Type III IFN or IFN-inducible genes
Select Ligand(s) for TLR1/TLR2Source
Triacyl lipopeptidesBacteria
Select Ligand(s) for TLR2Source
LipoproteinsMultiple pathogens
Peptidoglycan (PGN)Bacteria
PorinsBacteria
ZymosanFungi
beta-GlycanFungi
GPI-mucinProtozoa
Envelope glycoproteinsViruses
Select Ligand(s) for TLR3Source
Double-stranded RNAViruses
Poly (I:C)Synthetic analog
of ds-RNA
Select Ligand(s) for TLR4Source
Lipopolysaccharides (LPS)Bacteria
GlycoinositolphospholipidsProtozoa
Envelope glycoproteinsViruses
Select Ligand(s) for TLR5Source
FlagellinBacteria
Select Ligand(s) for TLR2/TLR6Source
Diacyl lipopeptidesBacteria
Lipoteichoic acid (LTA)Bacteria
Select Ligand(s) for TLR7Source
Single-stranded RNAViruses
Select Ligand(s) for TLR8Source
Single-stranded RNAViruses
Select Ligand(s) for TLR9Source
Bacteria
Unmethylated CpG DNAProtozoa
Viruses
Select Ligand(s) for TLR10Source
UnknownUnknown

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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