Fig. 5

Endosomal TLR 7 and 9 inhibition by HCQ and CQ: Mammalian Toll-like receptors (TLR) 7 and 9 initiate immune response when it encounters microbial nucleic acids (only shown here is a viral particle). The ectodomain of TLR 7 and 9 are cleaved in the endolysosome (not shown) which then recruits MYD88, followed by the activation of IRAK, TRAF6, and NF-kB. NF-kB then migrates to the nucleus and triggers the transcription of inflammatory cytokines. Both HCQ and CQ can increase the pH of the endolysosome and interfere with the TLR 9 and TLR 7 cleavage and processing. Furthermore, HCQ and CQ can directly bind to the microbial nucleic acids and prevent TLR-ligand interaction