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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...

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Autores principales: Guiducci, Cristiana, Ott, Gary, Chan, Jean H., Damon, Emily, Calacsan, Carlo, Matray, Tracy, Lee, Kyung-Dall, Coffman, Robert L., Barrat, Franck J.
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
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.
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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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