Review
Copyright ©The Author(s) 2016.
World J Hepatol. Nov 18, 2016; 8(32): 1354-1369
Published online Nov 18, 2016. doi: 10.4254/wjh.v8.i32.1354
Table 1 Toll-like receptor expression and their signaling in the liver[5,9,11,15,23,33,49]
TLR subfamilyMembersExpression of cell population in the liver (protein level)LocationLigand (origin)SignalingFinal product-effect
TLR2 subfamilyTLR1/2NK cells, DCs (h)Plasma membraneBacterial lipoproteins Triacylated lipopeptidesTIRAP-MyD88-NF-κB/AP-1/IRF5 pathwayPro- and anti-inflammatory cytokines excluding type 1 IFNs; the apoptotic cascade via recruiting FADD leading to caspase-8 activation
TLR2/6Hepatocytes, Kupffer cells, NK cells, B cells, activated T cells, DCs (m), biliary epithelial cellsDiacylated lipopeptides LPS of Gram-positive bacteria Fungal zymosan Mycoplasma lipopeptidesTIRAP-MyD88-NF-κB/AP-1 pathway
TLR10UnknownND
TLR3 subfamilyTLR3Hepatocytes, LSECs, Kupffer cells, NK cells, NKT cells, activated T cells, cDCs (m), biliary epithelial cellsEndosomeDouble-stranded RNA (viruses)PI3K/TRIF-IRF3 pathway TRAM-TRIF-NF-κB pathway PI3K/TRIF-RIP1-NF-κB pathwayProduction of type 1 IFNs; the apoptotic cascade via recruiting FADD leading to caspase 8 activation; DC maturation
TLR4 subfamilyTLR41Hepatocytes, LSECs, Kupffer cells, NK cells, B cells, activated T cells, DCs (m), biliary epithelial cells, HSCsPlasma membraneLPS of Gram-negative bacteria; fusion protein (respiratory syncytial virus), envelope protein (mouse mammary-tumor virus); HMGB1, hyaluronan, HSP60, free fatty acids (endogenous ligands); HSP72 (cells during stress and injury) surfactant protein A; fibrinogen; fibronectin extra domain ATIRAP-MyD88-NF-κB/AP-1 pathway TRAM-TRIF-NF-κB/IRF3 pathwayPro- and anti-inflammatory cytokines excluding type 1 IFNs; the apoptotic cascade via recruiting FADD leading to caspase 8 activation; DC maturation; activating caspase-1 through adaptor molecule apoptosis associated speck-like protein2
TLR5 subfamilyTLR5Biliary epithelial cellsPlasma membraneFlagellin protein (bacteria)MyD88-NF-κB/IRF5 pathwayPro- and anti-inflammatory cytokines excluding type 1 IFNs
TLR9 subfamilyTLR7/8NK cells, B cells, DCs (h), DCs (m)EndosomeSingle-stranded RNA (viruses), double-stranded, shortinterfering RNA (siRNA)MyD88 and endosomal acidification (maturation)-IRF7 pathway; MyD88- NF-κB pathwayHigh levels of type 1 IFN production in pDCs; proinflammatory cytokine production
TLR9LSECs, Kupffer cells, NK cells, B in mDCs and macrophagesImidazoquinoline CpG-containing viral or bacterial DNA Endogenous host-DNA