Fig. 2.

TLR intracellular localization and signaling. TLR3, TLR7, TLR8, and TLR9 are located on the membranes of intracellular compartments, such as the endoplasmic reticulum and endosomes. The myeloid differentiation primary response gene 88 (MYD88) is the one of the functional adapter molecules that have been reported to interact with all TLRs except TLR3. MYD88 recruits IL-IRAK1, IRAK2, IRAK4, and tumor necrosis factor–receptor associated factor 6 (TRAF6), leading ultimately to NF-κB activation and proinflammatory cytokine secretion and an inflammatory response. UNC93B1 is a multitransmembrane-domain-containing protein and plays a critical role in trafficking TLR7 and TLR9 from the endoplasmic reticulum to endosomes, where TLR7 and TLR9 transmit signals via MYD88/TRIF-dependent pathways (Kim et al., 2008).