TLR3, 7, 8 and 9 activation occurs within acidified endolysosomal compartments. Inhibition of endosome acidification with bafilomicin A or chloroquine abrogated TLR's-mediated responses to pathogen-derived nucleic acids (Hacker H et al 1998, Funami K et al 2004, Gibbard RJ et al 2006, Kuznik A et al 2011). Upon stimulation, TLR3, 7, and 9 (and possibly TLR8) are transported to the signaling endosomes by UNC93B1, whereby they become functional receptors and bind to their specific ligands (Kim et al 2008, Ewald et al 2011). Although UNC93B1 is critically involved in TLRs trafficking it was dispensable for ligand binding by these TLRs (Kim YM et al 2008).
Latz, E, Schoenemeyer, A, Visintin, A, Fitzgerald, KA, Monks, BG, Knetter, CF, Lien, E, Nilsen, NJ, Espevik, T, Golenbock, DT
Gibbard, RJ, Morley, PJ, Gay, NJ
Hacker, H, Mischak, H, Miethke, T, Liptay, S, Schmid, R, Sparwasser, T, Heeg, K, Lipford, GB, Wagner, H
Funami, K, Matsumoto, M, Oshiumi, H, Akazawa, T, Yamamoto, A, Seya, T
Kim, YM, Brinkmann, MM, Paquet, ME, Ploegh, HL
Ewald, SE, Engel, A, Lee, J, Wang, M, Bogyo, M, Barton, GM
Kuznik, A, Bencina, M, Svajger, U, Jeras, M, Rozman, B, Jerala, R
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