| TLRs that recognize bacterial and fungal cell wall components, such as TLR4–MD-2, TLR5 and the heterodimers TLR2+TLR1 and TLR2+TLR6, are localized to the plasma membrane and can recognize ligands there. They are also delivered to nascent phagosomes, apparently by a mechanism that is independent of ligand binding. In contrast, TLRs recognizing nucleic acids (TLR3, TLR7, TLR8 and TLR9) are primarily or completely contained in intracellular membranes and unavailable for interaction with extracellular ligands. It is believed that these TLRs are delivered to phagolyosomes or late endosomes. Ligand recognition by these TLRs can often be blocked by agents that block the acidification of endosomes or phagosomes, such as chloroquine. |
