AUTHOR=Petes Carlene , Odoardi Natalya , Gee Katrina TITLE=The Toll for Trafficking: Toll-Like Receptor 7 Delivery to the Endosome JOURNAL=Frontiers in Immunology VOLUME=8 YEAR=2017 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2017.01075 DOI=10.3389/fimmu.2017.01075 ISSN=1664-3224 ABSTRACT=

Toll-like receptor (TLR)-7 is an endosomal innate immune sensor capable of detecting single-stranded ribonucleic acid. TLR7-mediated induction of type I interferon and other inflammatory cytokine production is important in antiviral immune responses. Furthermore, altered TLR7 expression levels are implicated in various autoimmune disorders, indicating a key role for this receptor in modulating inflammation. This review is focused on the regulation of TLR7 expression and localization compared to that of the other endosomal TLRs: TLR3, 8, and 9. Endosomal TLR localization is a tightly controlled and intricate process with some shared components among various TLRs. However, TLR-specific mechanisms must also be in place in order to regulate the induction of pathogen- and cell-specific responses. It is known that TLR7 is shuttled from the endoplasmic reticulum to the endosome via vesicles from the Golgi. Several chaperone proteins are required for this process, most notably uncoordinated 93 homolog B1 (Caenorhabditis elegans), recently identified to also be involved in the localization of the other endosomal TLRs. Acidification of the endosome and proteolytic cleavage of TLR7 are essential for TLR7 signaling in response to ligand binding. Cleavage of TLR7 has been demonstrated to be accomplished by furin peptidases in addition to cathepsins and asparagine endopeptidases. Moreover, triggering receptor expressed on myeloid cells like 4, a protein associated with antigen presentation and apoptosis in immune cells, has been implicated in the amplification of TLR7 signaling. Understanding these and other molecular mechanisms controlling TLR7 expression and trafficking will give insight into the specific control of TLR7 activity compared to the other endosomal TLRs.