1. Definition
Toll-like receptors (TLRs) are a class of pattern recognition receptors (PRRs) that play a crucial role in the innate immune system by recognizing pathogen-associated molecular patterns (PAMPs) found in microbes. They trigger immune responses by activating signaling pathways that lead to the production of cytokines and other immune mediators.
2. Classification
Toll-like receptors (TLRs) are classified into different types based on the specific pathogen-associated molecular patterns (PAMPs) they recognize and their location within the cell. There are 10 functional TLRs in humans (TLR1 to TLR10).
Surface TLRs (Detect extracellular pathogens):
- TLR1: Forms a heterodimer with TLR2 to recognize triacyl lipopeptides found in bacteria.
- TLR2: Recognizes a wide variety of ligands, including lipoproteins and peptidoglycan from gram-positive bacteria, fungi, and viruses (often forms heterodimers with TLR1 or TLR6).
- TLR4: Primarily recognizes lipopolysaccharide (LPS) from gram-negative bacteria.
- TLR5: Recognizes flagellin, a protein found in bacterial flagella.
- TLR6: Forms a heterodimer with TLR2 to recognize diacyl lipopeptides from mycoplasma and certain gram-positive bacteria.
Endosomal TLRs (Detect intracellular pathogens, such as viral RNA or DNA):
- TLR3: Recognizes double-stranded RNA (dsRNA), often associated with viral infections.
- TLR7: Recognizes single-stranded RNA (ssRNA) from viruses, especially RNA viruses.
- TLR8: Similar to TLR7, it recognizes viral single-stranded RNA.
- TLR9: Recognizes unmethylated CpG DNA sequences commonly found in bacterial and viral DNA.
- TLR10: Its function is less well-defined, but it is thought to have anti-inflammatory roles and may detect endogenous or pathogen-derived ligands.
3. Cells
1. Immune Cells:
- Macrophages: Express multiple TLRs (e.g., TLR2, TLR4, TLR5, TLR9).
- Dendritic Cells (DCs): Both plasmacytoid and myeloid dendritic cells express TLRs, such as TLR3, TLR7, TLR8, and TLR9.
- Neutrophils: Express TLR2, TLR4, and TLR5.
- B Cells: Express TLR9, which helps them recognize unmethylated CpG DNA, and TLR4 in some cases.
- T Cells: Generally express fewer TLRs than innate immune cells, but some subsets, like regulatory T cells and memory T cells, may express TLR2 and TLR4.
- Natural Killer (NK) Cells: Can express TLR3, TLR7, and TLR8.
2. Non-Immune Cells:
- Epithelial Cells: Found in barrier tissues such as the skin, respiratory, gastrointestinal, and urogenital tracts, these cells express TLRs (e.g., TLR2, TLR4, TLR5)
- Endothelial Cells: These cells, lining blood vessels, express TLRs such as TLR2 and TLR4
- Fibroblasts: These structural cells can express TLRs (e.g., TLR2, TLR3)