Table 2.
Pattern recognition receptors: TLRs and NLRs.
| Receptor | Cellular location | Tissue location | Intracellular Mechanism | MAMPs | DAMPs |
|---|---|---|---|---|---|
| TLR2 | Plasma membrane | CNS: Microglia, astrocytes and oligodendrocytes (93) GI: Mononuclear cells of the lamina propria, goblet cells, enterocytes, and neurons from the ENS (94, 95) |
TLR2 forms heterodimers with TLR1 and TLR6 to detect most of its specific ligands. Then, it generally triggers a MyD88-dependent signaling pathway to promote the translocation of nuclear factor-B that regulate the synthesis of inflammatory factors (96) | Molecules with diacyl and triacylglycerol moieties, proteins, and polysaccharides (96) | HSP60 and HSP70 (97) HMGB1 (98) Gp96 (99) |
| TLR3 | Endosomal membrane | CNS: Astrocytes, oligodendrocytes, and microglia cells (93) GI: Immune cells of lamina propria and IECs including goblet cells and enterocytes (100) and in neurons from ENS (101). |
TLR3 activation triggers TRIF/TICAM1 intracellular signaling that ends in the NF-kappa-B activation with IRF3 nuclear translocation and the synthesis and release of inflammatory factors (102) | Double-stranded (ds) RNA (103) | Endogenous mRNA from inflammation (104) |
| TLR4 | Plasma membrane | CNS: Microglia cells (105), astrocytes (106) GI: Immune cells of lamina propria, in the apical membrane of IECs in small intestine and in the basolateral membrane in the colon (107). Moreover, it can be found in neurons from ENS (101) |
TLR4 can trigger a Myd88-dependent signaling pathway and a Myd88-independent intracellular signaling pathway driven by TRIF to promote the translocation of nuclear factor-B that regulate the synthesis of inflammatory factors (108) | Lipopolysaccharide (109) | HMGB1 (110) Fibrinogen (111) HSP60, HSP72, SP22 (112) Lactoferrin (113) |
| TLR5 | Plasma membrane | CNS: Microglia cells (93) GI: Basolateral side of IECs at the colon, at Paneth cells at the small intestine while in small intestine its expression is restricted to Paneth cells. |
TLR5 activation triggers MYD88 and TRIF intracellular signaling that leads to the translocation of NF-kappa-B and inflammatory response (114, 115) | Flagellin (116) | HMGB1 (117) Hyaluronan (118) |
| TLR7 | Endosomal membrane | CNS: Microglia cells (93) GI: IECs, plasmacytoid dendritic cells (pDCs), B cells at the lamina propria (119), and in the myenteric and submucous plexuses of murine intestine and human ileum (101). |
TLR7 activation triggers MYD88 intracellular pathway signaling that leads to the activation NF-kappa-B and IRF7 to promote the synthesis of inflammatory factors (120) | ssRNA (121) | Guanosine and short O(R)Ns from RNA degradation (122) ssRNA (123) |
| TLR8 | Endosomal membrane | CNS: Microglia cells (93) GI: Macrophages and monocyte-derived DCs at lamina propria (121) |
TLR8 activation recruits MYD88 intracellular pathway signaling that activates NF-kappa-B and IRF7 to promote the synthesis of inflammatory factors (124) | ssRNA (121) | ssRNA (123) Uridine and short ORNs from RNA degradation (122) |
| TLR9 | Endosomal membrane/Plasma membrane | CNS: Microglia, neurons, and astrocytes (125) GI: Immune cells from lamina propria in GI epithelial cells (119) |
TLR9 activation induce MYD88 and TRAF intracellular pathway downstream that leads into the activation of NF-kappa-B (126) | Unmethylated cytidine-phosphate-guanosine (CpG) dinucleotides (127) | IgG–chromatin complexes (128) Host DNA degradation (129) |
| TLR10 | Plasma membrane | CNS: Microglia (130) GI: B-cells (131) and IECs (132) |
TLR10 may trigger intracellular responses MyD88-dependent and MYD88-independent downstream signaling (132) | Unknown MAMPs Candidates as a TLR10 ligand: diacylated lipopeptides (133) and lipopolysaccharide (133) |
Unknown DAMPs |
| NOD1 | Intracellular compartment | CNS: Microglia (134), neurons, and astrocytes at prefrontal cortex, hippocampus, and cerebellum (135) GI: IECs and in the immune cells from lamina propria (136) |
NOD1 recruits RIPK2, which promotes interactions with TRAF, and activates the expression NF-κB and MAPK involved in inflammatory responses (137) |
κ-d-glutamyl-meso-diaminopimelic acid (136) | Endoplasmic reticulum stress molecules (138) Calcium (138) |
| NOD2 | Intracellular compartment | CNS: Microglia (134) GI: Monocytes, dendritic cells, epithelial cells, Paneth cells, and intestinal stem cells (139) |
NOD2 recruits RIPK2, which promotes interactions with TRAF, and activates the expression NF-κB and MAPK involved in inflammatory responses (137) | Muramyl dipeptide (140) | Endoplasmic reticulum stress molecules (138) Calcium (138) |
Indication of intracellular location, expression at the central nervous system (CNS) and gastrointestinal tract (GI), main intracellular mechanism, main microbial-associated molecular patterns (MAMPs), and main damage-associated molecular patterns (DAMPs).