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Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation
Human plasmacytoid dendritic cells (PDCs) can produce interferon (IFN)-α and/or mature and participate in the adaptive immune response. Three classes of CpG oligonucleotide ligands for Toll-like receptor (TLR)9 can be distinguished by different sequence motifs and different abilities to stimulate IF...
Autores principales: | , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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The Rockefeller University Press
2006
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118381/ https://www.ncbi.nlm.nih.gov/pubmed/16864658 http://dx.doi.org/10.1084/jem.20060401 |
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author | Guiducci, Cristiana Ott, Gary Chan, Jean H. Damon, Emily Calacsan, Carlo Matray, Tracy Lee, Kyung-Dall Coffman, Robert L. Barrat, Franck J. |
author_facet | Guiducci, Cristiana Ott, Gary Chan, Jean H. Damon, Emily Calacsan, Carlo Matray, Tracy Lee, Kyung-Dall Coffman, Robert L. Barrat, Franck J. |
author_sort | Guiducci, Cristiana |
collection | PubMed |
description | Human plasmacytoid dendritic cells (PDCs) can produce interferon (IFN)-α and/or mature and participate in the adaptive immune response. Three classes of CpG oligonucleotide ligands for Toll-like receptor (TLR)9 can be distinguished by different sequence motifs and different abilities to stimulate IFN-α production and maturation of PDCs. We show that the nature of the PDC response is determined by the higher order structure and endosomal location of the CpG oligonucleotide. Activation of TLR9 by the multimeric CpG-A occurs in transferrin receptor (TfR)-positive endosomes and leads exclusively to IFN-α production, whereas monomeric CpG-B oligonucleotides localize to lysosome-associated membrane protein (LAMP)-1–positive endosomes and promote maturation of PDCs. However, CpG-B, when complexed into microparticles, localizes in TfR-positive endosomes and induces IFN-α from PDCs, whereas monomeric forms of CpG-A localize to LAMP-1–positive endosomes accompanied by the loss of IFN-α production and a gain in PDC maturation activity. CpG-C sequences, which induce both IFN-α and maturation of PDCs, are distributed in both type of endosomes. Encapsulation of CpG-C in liposomes stable above pH 5.75 completely abrogated the IFN-α response while increasing PDC maturation. This establishes that the primary determinant of TLR9 signaling is not valency but endosomal location and demonstrates a strict compartmentalization of the biological response to TLR9 activation in PDCs. |
format | Text |
id | pubmed-2118381 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2006 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-21183812007-12-13 Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation Guiducci, Cristiana Ott, Gary Chan, Jean H. Damon, Emily Calacsan, Carlo Matray, Tracy Lee, Kyung-Dall Coffman, Robert L. Barrat, Franck J. J Exp Med Articles Human plasmacytoid dendritic cells (PDCs) can produce interferon (IFN)-α and/or mature and participate in the adaptive immune response. Three classes of CpG oligonucleotide ligands for Toll-like receptor (TLR)9 can be distinguished by different sequence motifs and different abilities to stimulate IFN-α production and maturation of PDCs. We show that the nature of the PDC response is determined by the higher order structure and endosomal location of the CpG oligonucleotide. Activation of TLR9 by the multimeric CpG-A occurs in transferrin receptor (TfR)-positive endosomes and leads exclusively to IFN-α production, whereas monomeric CpG-B oligonucleotides localize to lysosome-associated membrane protein (LAMP)-1–positive endosomes and promote maturation of PDCs. However, CpG-B, when complexed into microparticles, localizes in TfR-positive endosomes and induces IFN-α from PDCs, whereas monomeric forms of CpG-A localize to LAMP-1–positive endosomes accompanied by the loss of IFN-α production and a gain in PDC maturation activity. CpG-C sequences, which induce both IFN-α and maturation of PDCs, are distributed in both type of endosomes. Encapsulation of CpG-C in liposomes stable above pH 5.75 completely abrogated the IFN-α response while increasing PDC maturation. This establishes that the primary determinant of TLR9 signaling is not valency but endosomal location and demonstrates a strict compartmentalization of the biological response to TLR9 activation in PDCs. The Rockefeller University Press 2006-08-07 /pmc/articles/PMC2118381/ /pubmed/16864658 http://dx.doi.org/10.1084/jem.20060401 Text en Copyright © 2006, The Rockefeller University Press This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Articles Guiducci, Cristiana Ott, Gary Chan, Jean H. Damon, Emily Calacsan, Carlo Matray, Tracy Lee, Kyung-Dall Coffman, Robert L. Barrat, Franck J. Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation |
title | Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation |
title_full | Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation |
title_fullStr | Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation |
title_full_unstemmed | Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation |
title_short | Properties regulating the nature of the plasmacytoid dendritic cell response to Toll-like receptor 9 activation |
title_sort | properties regulating the nature of the plasmacytoid dendritic cell response to toll-like receptor 9 activation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118381/ https://www.ncbi.nlm.nih.gov/pubmed/16864658 http://dx.doi.org/10.1084/jem.20060401 |
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