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. Author manuscript; available in PMC: 2014 Mar 9.
Published in final edited form as: Front Biosci (Landmark Ed). 2011 Jun 1;16:2060–2068. doi: 10.2741/3839

FIGURE 1. MULTIPLE LEVELS OF ENDOSOMAL TLR REGULATION.

FIGURE 1

Nucleotides are sensed by TLRs in endolysosomes in order to allow for the efficient discrimination between pathogen-associated and self-derived nucleic acids. Viral genomes are protected by their capsids until they are released within the endolysosomal compartment, whereas extracellular self-derived nucleic acids are degraded by DNases before reaching endolysosomes. Endosomal TLR responses are also limited by controlling their intracellular trafficking. Endosomal TRLs associate with gp96, PRAT4A, and UNC93B1 in the ER. These chaperone proteins facilitate the transport of intracellular TLRs through the Golgi via the conventional secretory pathway to the endolysosome (denoted by (1)). In some instances, however, full length TLRs may be trafficked to the plasma membrane (denoted by (2)). These mislocalized TLRs cannot signal since they are not processed to their active form at the plasma membrane like they are in the endolysosomal compartment by proteases, such as cathepsins.