Table 1.
Comparative presentation of endosomal TLRs and their ligands, enzymes required for cleavage, the importance of cleavage and eventual participation of cleaved fragments in signaling, and the possibility of occurrence on the surface of cells.
| Endosomal TLR | Ligand | Enzymes responsible for cleavage | Cleavage required for TLR signaling | The ability of full-length/cleaved fragments to bind ligand | The requirement of C and N association for signal transduction | Occurrence on the surface of the cell |
|---|---|---|---|---|---|---|
| TLR3 | double-stranded RNA | cathepsins B, L, and/or S (48), H (66) |
not required (but may modulate the level of antiviral response) (48)/ required (66) |
present: FL, N, C (48) |
required (56, 69) | yes: CD8+ DCs, MZ B cells, J774 macrophages, BM-MCs (56), HEK293T cells (48), prostate epithelium (70), human conjunctival fibroblasts (HCF) (71), apical and basal plasma membrane of human endocervical cells (72), rat peritoneal mast cells (73, 74), and other |
| TLR7 | single-stranded RNA, guanosine | cathepsin B* (65), asparagine endopeptidase (AEP) (75), furin-like proprotein convertases (76) |
not required (64)/ required (30, 75, 77, 78) |
present: FL, C (75), C (78), N, C (cooperatively involved) (30) |
not required (75)/ required (30, 78) |
yes: BM-DM, BM-conventional DCs, BM-plasmacytoid DCs, B cells, peripheral blood mononuclear cells (14), rat peritoneal mast cells (73, 74) |
| TLR8 | uridine-rich or uridine/guanosine-rich single-stranded RNA | cathepsins*, furin-like proprotein convertase (79) | required** (68, 79) | present**: N, C (68, 79) |
required** (68, 79) | unknown |
| TLR9 | unmethylated CpG DNA | cathepsin B (63), F (63), K (62, 77), L (63, 64), S (63, 64, 77), AEP (80) | required (48, 64, 77, 80, 81) | present: FL, N, C (64, 77, 80) |
not required (the cleaved 80 kDa form is considered to constitute a mature receptor) (80)/ required (54) |
yes: conventional DCs and plasmacytoid DCs (pDCs) (54), rat peritoneal mast cells (73, 74), PBMCs (82), IECs (83), neutrophils (84), human hepatocellular carcinoma (HCC) cell lines (85), B cells (86), splenic monocytes and B cells, RAW 264.7 cells (87) |
The features discussed are presented at the top of each column. FL, full-length; C, C-terminal; N, N-terminal. *studies were carried out indirectly, with the use of cathepsin inhibitor, which can exert broader activity; **result obtained on the basis of structural analysis studies.