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. 2020 Apr 23;11:724. doi: 10.3389/fimmu.2020.00724

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Copyright © 2020 Yang, Wise and Fukuchi.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

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Toll-like receptor pathways. TLR1, TLR2, TLR4, TLR5, and TLR6 are mostly expressed on the cell surface and bind to bacterial products. When activated by LPS, TLR4 is internalized onto an endosome surface. The internalization triggers the release of TIRAP/MyD88, activating the TRAF6 pathway and resulting in activation of transcription factors, NF-_kB and AP-1. The release of TIRAP/MyD88 from TLR4 allows for the signaling by TRAM/TRIF to commence from the endosome, also activating NF-_kB as well as the transcription factor, IRF3. TLR3, TLR7, TLR8, and TLR9 are located on internal vesicles and bind to bacterial and viral nucleic acids. TLR7, TLR8, and TLR9 each activate NF-_kB, as well as the transcription factor, IRF7, through the MyD88 pathway. TLR3 is the only toll-like receptor that does not activate via the MyD88 pathway and instead activates NF-_kB and IRF3 through the TRIF pathway.