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The Toll for Trafficking: Toll-Like Receptor 7 Delivery to the Endosome

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 i...

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Autores principales: Petes, Carlene, Odoardi, Natalya, Gee, Katrina
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591332/
https://www.ncbi.nlm.nih.gov/pubmed/28928743
http://dx.doi.org/10.3389/fimmu.2017.01075
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author Petes, Carlene
Odoardi, Natalya
Gee, Katrina
author_facet Petes, Carlene
Odoardi, Natalya
Gee, Katrina
author_sort Petes, Carlene
collection PubMed
description 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.
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spelling pubmed-55913322017-09-19 The Toll for Trafficking: Toll-Like Receptor 7 Delivery to the Endosome Petes, Carlene Odoardi, Natalya Gee, Katrina Front Immunol Immunology 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. Frontiers Media S.A. 2017-09-04 /pmc/articles/PMC5591332/ /pubmed/28928743 http://dx.doi.org/10.3389/fimmu.2017.01075 Text en Copyright © 2017 Petes, Odoardi and Gee. http://creativecommons.org/licenses/by/4.0/ 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) or licensor 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.
spellingShingle Immunology
Petes, Carlene
Odoardi, Natalya
Gee, Katrina
The Toll for Trafficking: Toll-Like Receptor 7 Delivery to the Endosome
title The Toll for Trafficking: Toll-Like Receptor 7 Delivery to the Endosome
title_full The Toll for Trafficking: Toll-Like Receptor 7 Delivery to the Endosome
title_fullStr The Toll for Trafficking: Toll-Like Receptor 7 Delivery to the Endosome
title_full_unstemmed The Toll for Trafficking: Toll-Like Receptor 7 Delivery to the Endosome
title_short The Toll for Trafficking: Toll-Like Receptor 7 Delivery to the Endosome
title_sort toll for trafficking: toll-like receptor 7 delivery to the endosome
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5591332/
https://www.ncbi.nlm.nih.gov/pubmed/28928743
http://dx.doi.org/10.3389/fimmu.2017.01075
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