TLR-12 is also expressed in macrophages and dendritic cells, and is more broadly expressed in hematopoietic cells than TLR-11, but is not expressed by the epithelial tissues where TLR-11 is expressed. TLR-11-deficient mice develop urinary infections caused by uropathogenic strains of Escherichia coli, although the bacterial ligand for TLR-11 has not yet been identified. TLR-11 and TLR-12 have an overlapping function in that both recognize protozoan parasites such as Toxoplasma gondii and Plasmodium falciparum. They bind to protein motifs that are present in the protozoan actin-binding protein profilin but absent in mammalian profilins. TLR-11 and TLR-12 are both required in macrophages and conventional dendritic cells for activation by T. gondii profilin, but TLR-12 plays a more dominant role. Mice lacking TLR-11 develop more severe tissue injury than normal mice on infection with
Fig. 3.12 Direct recognition of pathogen-associated molecular can activate TLR1:TLR2 dimers; it has three fatty-acid chains bound patterns by TLR-1 and TLR-2 induces dimerization of the TLRs to a polypeptide backbone. Two fatty-acid chains bind to a pocket and signaling. TLR-1 and TLR-2 are located on cell surfaces (left on the convex surface of the TLR-2 ectodomain, and the third chain panel), where they can directly recognize bacterial triacyl lipoproteins associates with a hydrophobic channel in the convex binding surface (middle panel). The convex surfaces of their extracellular domains of TLR-1, inducing dimerization of the two TLR subunits and bringing have binding sites for the lipid side chains of triacyl lipopeptides. In their cytoplasmic Toll–IL-1 receptor (TIR) domains together to initiate the crystal structure (right panel), the ligand is a synthetic lipid that signaling. Structure courtesy of Jie-Oh Lee.
Pattern recognition by cells of the innate immune system.
Toxoplasma, whereas mice lacking TLR-12 die rapidly after infection. TLR-10 is expressed in humans, but TLR-10 is a pseudogene in mice. Its ligand and function are currently not known.