Table 1.
TLR expression in CNS resident cell subsets. CNS: Central nervous system, DRG: Dorsal root ganglia, EP: Envelope protein, FC: Flow cytometry, GP: Glycoprotein, hiPSC: Human induced pluripotent stem cell, ICC: Immunocytochemistry, IF: Immunofluorescence, IR: Immunoreactivity, LTA: Lipoteichoic acid, LPS: Lipopolysaccharide, PGN: Peptidoglycan, RNAseq: RNA sequencing, RT-PCR: Reverse transcription PCR, WB: Western blot. +: Expressed, −: Not expressed.
| Receptor | Ligand | Expression on CNS-Resident Cells | |||||
| Mouse | Human | ||||||
| Neurons | Astrocytes | Microglia | Neurons | Astrocytes | Microglia | ||
| TLR1 [41] |
Bacterial lipo-proteins [41] |
+ IF (in vivo) [111] |
+ RT-PCR (in vitro, primary astrocytes), IF (in vivo) [111,112] |
+ IF (in vivo) [111] |
+ RT-PCR (in vitro, cell line) [113,114] |
+ (low) RT-PCR (in vitro, primary astrocytes) [115] |
+ RT-PCR (in vitro, primary microglia) [108,115] |
| TLR2 [35] |
PGN, LTA [116,117], viral EPs, GPs, core proteins | + IF (in vivo), IF (in vitro, primary cortical neurons) [118,119] |
+ RT-PCR, FC, WB (in vitro, primary astrocytes), FC (ex vivo) [112,120,121] |
+ RT-PCR (in vitro, cell line), FC (ex vivo) [121,122] |
+ RT-PCR (in vitro, cell lines) [113,114,122] |
+ (low) RT-PCR (in vitro, primary astrocytes) [108,115] |
+ RT-PCR, IF (in vitro, primary microglia) [108,115] |
| TLR3 [34] |
dsRNA, poly(I:C) [34] |
+ FC (in vitro, primary neurons) [70] |
+ RT-PCR, FC (in vitro, primary astrocytes) [70,112] |
+ RT-PCR (in vitro, cell line), FC (in vitro, primary microglia) [70,122] |
+ RT-PCR (in vitro, primary neurons and cell lines), WB (in vitro, hiPSC neurons) [113,114,122,123] |
+ RT-PCR, FC (in vitro, primary astrocytes) [108,115] |
+ (low) RT-PCR, FC (in vitro, primary microglia) [108,115] |
| TLR4 [33,124] |
LPS [33,124], GPs, EPs, fusion proteins [47,48] | + RT-PCR (in vitro, primary neurons) [125] |
+ RT-PCR, FC (in vitro, primary astrocytes) [112,120,125] |
+ RT-PCR, WB (in vitro, cell line), RT-PCR (in vitro, primary microglia) [122,125] |
+ RT-PCR, WB (in vitro, cell lines and primary microglia) [113,114,122] |
+ (low) RT-PCR (in vitro, primary astrocytes) [115] |
+ RT-PCR, IF (in vitro, primary microglia) [108,115] |
| TLR5 [37] |
Flagellin, profilin [37] |
− IF (in vitro, primary neurons) [126] + microarray (in vitro, primary cortical neurons) [118] |
+ RT-PCR, IF (in vitro, primary astrocytes) [112,120,126] |
+ IF (in vitro, primary microglia) [126] |
+ RT-PCR (in vitro, primary neurons) [114] |
+ (low) RT-PCR (in vitro, primary astrocytes) [115] |
+ (low) RT-PCR (in vitro, primary microglia) [108,115] |
| TLR6 [40] |
Diacyl lipo-peptides [40] |
+ IF (in vitro, primary DRG neurons) [127] |
+ RT-PCR (in vitro, primary astrocytes), FC (ex vivo) [112,121] |
− FC (ex vivo) [121] |
+ RT-PCR (in vitro, primary neurons and cell lines ) [114] |
+ (low) RT-PCR (in vitro, primary astrocytes) [115] |
+ (low) RT-PCR (in vitro, primary microglia) [108,115] |
| TLR7 [36,38] |
ssRNA [36,38] |
+ WB, RT-PCR (in vitro, primary DRG and CNS neurons) [128,129] |
− RT-PCR (in vitro, primary astrocytes) [112] |
+ RT-PCR (in vitro, cell line) [122] |
+ (low) RT-PCR (in vitro, cell lines and primary neurons) [114,122] |
+ (low) RT-PCR (in vitro, primary astrocytes) [115] |
+ RT-PCR (in vitro, primary microglia) [108,115] |
| TLR8 [38] |
ssRNA [38] |
+ WB, RT-PCR (in vitro, primary DRG and CNS neurons) [128,129] |
− RT-PCR (in vitro, primary astrocytes) [112] |
+ RT-PCR (in vitro, cell line) [122] |
+ (low) RT-PCR (in vitro, cell lines and primary neurons) [114,122] |
− RT-PCR (in vitro, primary astrocytes) [115] |
+ (low) RT-PCR (in vitro, primary microglia) [108,115] |
| TLR9 [39] |
Unmethylated CpG DNA [39] |
+ IF, WB, RT-PCR (in vitro, primary neurons) [130] |
+ (low) RT-PCR (in vitro, primary astrocytes) Very low on basal level [120], present upon inflammatory stimulation [112,120] |
+ WB (ex vivo) [131] |
+ RT-PCR (in vitro, primary cells, cell line) [114] − RT-PCR (in vitro, cell line) [113] |
+ (low) RT-PCR (in vitro, primary astrocytes) [115] |
+ (low) RT-PCR (in vitro, primary microglia) [115] |
| TLR10 [132] |
Triacyl lipopeptides, flagellin [133], EPs, RNA [134] | - | - | - | + RT-PCR (in vitro, primary neurons) [114] − RT-PCR (in vitro, cell line) [113] |
+ (low) RT-PCR (in vitro, primary astrocytes) [115] |
− RT-PCR (in vitro, primary microglia) [115] + RNAseq (ex vivo) [135] |
| TLR11 [43] |
Profilin [136] |
+ In situ IF (in vivo) [137] |
− In situ IF (in vivo) [137] |
− In situ IF (in vivo) [137] |
- | - | - |
| TLR12 [138] |
Profilin [138] |
+ In situ IF (in vivo) [137] |
− In situ IF (in vivo) [137] |
− In situ IF (in vivo) [137] |
- | - | - |
| TLR13 [44] |
Unmethylated bacterial RNA [44] | + In situ IF (in vivo) [137] |
+ In situ IF (in vivo) [137] |
+ (low) In situ IF (in vivo) [137] |
- | - | - |
| Adaptor | Connected TLR | Expression on CNS-Resident Cells | |||||
| Mouse | Human | ||||||
| Neurons | Astrocytes | Microglia | Neurons | Astrocytes | Microglia | ||
| MyD88 [139] |
TLR1, TLR2, TLR4-9, TLR11-13 | + IF (in vitro, primary neurons) [118] |
+ WB (in vitro) IF (in vivo, spinal cord astrocytes) [140] |
+ RT-PCR (in vitro, cell line), WB (in vitro, primary microglia and cell line) [122,141,142] |
+ RT-PCR, WB (in vitro, cell line) [122,143] |
+ RT-PCR (in vivo) [144] |
+ RNAseq (ex vivo) [135] |
| TRIF [145] |
TLR3, TLR4 |
+ IF, WB (in vivo, in vitro, primary hippocampal neurons) [146] |
+ (low) IF (in vivo) [146] |
+ (low) IF(in vivo), WB (in vitro, cell line) [142,146] |
+ IR (in vivo) [146] |
+ IR (in vivo) [146] |
+ IR (in vivo) [146] |