Page 53 - Veterinary Immunology, 10th Edition

such as macrophages, neutrophils, mast cells, and dendritic cells.
VetBooks.ir They are also found on T and B cells of the adaptive immune

system, as well as on nonimmune cells such as the epithelial cells
that line the respiratory and intestinal tracts. When activated they

turn on genes involved in producing proinflammatory factors. Thus
they trigger inflammation when they sense the presence of invaders
or tissue damage.
Mammals possess 10 or 12 different functional TLRs (TLRs 1 to 10

in humans, sheep and cattle and TLRs 1 to 9 and 11 to 13 in mice)
(Table 2.1). The cell surface TLRs (TLRs 1, 2, 4, 5, 6, and 11) mainly
bind bacterial and fungal proteins, lipoproteins, and
lipopolysaccharides. The intracellular TLRs (TLRs 3, 7, 8, 9, and 10),

bind viral and bacterial nucleic acids. For example, TLR4 on the cell
surface binds lipopolysaccharides from Gram-negative bacteria.
TLR2 binds peptidoglycans and lipoproteins from Gram-positive
bacteria and a glycolipid called lipoarabinomannan from

Mycobacterium tuberculosis. TLR5 binds flagellin, the major protein
of bacterial flagella. TLR9, in contrast, is an intracellular sensor of
bacterial DNA and is therefore triggered by intracellular bacteria.
Other intracellular receptors, such as TLR3, bind viral double-

stranded (ds) ribonucleic acid (RNA), whereas TLR7 and TLR8 bind
viral single-stranded (ss) RNA (Fig. 2.4).

TABLE 2.1
Pathogen-Associated Molecular Patterns and the Functions of

the Mammalian Toll-like Receptors

TLR Cell Location Ligand Pathogens Recognized
TLR1 Cell surface Triacylated lipoprotein Bacteria
TLR2 Cell surface Lipoproteins Bacteria, viruses, parasites
TLR3 Intracellular dsRNA Viruses
TLR4 Cell surface LPS Bacteria, viruses
TLR5 Cell surface Flagellin Bacteria
TLR6 Cell surface Diacylated lipoprotein Bacteria, viruses
TLR7 Intracellular ssRNA, guanosine Viruses, bacteria
TLR8 Intracellular ssRNA Viruses, bacteria
TLR9 Intracellular CpG DNA, dsDNA Viruses, bacteria, protozoa
TLR10 Intracellular Regulates TLR2 responses Suppresses inflammation
TLR11 Cell surface Profilin and flagellin Protozoa, bacteria
TLR12 Cell surface Profilin Protozoa
TLR13 Intracellular Unmethylated RNA Bacteria
CpG, cytosine-guanosine; LPS, lipopolysaccharide; TLR, toll-like receptor.

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