It’s what inside that counts for TLRs 7 & 9

Toll-like receptors (TLRs) help mammalian immune systems protect against infections by binding to molecular patterns that are characteristic of many dangerous microbes. The location of TLR7 and TLR9 within the cell, not on the cell surface, appears crucial to their distinguishing viral from host nucleic acids and maintaining self-tolerance.

Ewald and colleagues determined how these TLRs ‘traffic’ within macrophages and dendritic cells, which are dedicated to picking up and destroying matter, including viruses. They found that these TLRs, after their synthesis in the endoplasmic reticulum, move to vesicles called endolysosomes where recently-internalized materials are degraded. There, a portion of the TLR within the lumen of the lysosome, the 'ectodomain', is cut and destroyed. Both the full-length and ectodomain-cleaved TLRs can bind nucleic acids but only the proteolysed (cleaved) TLR can activate downstream signaling by recruiting MyD88 (Figure 4e shown, anti-Flag-tagged-TLR binds to and co-precipitates HA-tagged TLR after stimulation with nucleic acid). The authors propose that TLR proteolysis and activation within the endolysosome serves to restrict its exposure to 'self' molecules and thereby reduce the likelihood of triggering autoimmunity.

Ewald SE, Lee BL, Lau L, Wickliffe KE, Shi GP, Chapman HA, Barton GM. "The ectodomain of Toll-like receptor 9 is cleaved to generate a functional receptor." Nature. 2008 Dec 4;456(7222):658-62. Epub 2008 Sep 28.