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Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice

An emerging strategy in preventing and treating airway allergy consists of modulating the immune response induced against allergens in the lungs. CpG oligodeoxynucleotides have been investigated in airway allergy studies, but even if promising, efficacy requires further substantiation. We investigat...

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Autores principales: Ballester, Marie, Jeanbart, Laura, de Titta, Alexandre, Nembrini, Chiara, Marsland, Benjamin J., Hubbell, Jeffrey A., Swartz, Melody A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585708/
https://www.ncbi.nlm.nih.gov/pubmed/26387548
http://dx.doi.org/10.1038/srep14274
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author Ballester, Marie
Jeanbart, Laura
de Titta, Alexandre
Nembrini, Chiara
Marsland, Benjamin J.
Hubbell, Jeffrey A.
Swartz, Melody A.
author_facet Ballester, Marie
Jeanbart, Laura
de Titta, Alexandre
Nembrini, Chiara
Marsland, Benjamin J.
Hubbell, Jeffrey A.
Swartz, Melody A.
author_sort Ballester, Marie
collection PubMed
description An emerging strategy in preventing and treating airway allergy consists of modulating the immune response induced against allergens in the lungs. CpG oligodeoxynucleotides have been investigated in airway allergy studies, but even if promising, efficacy requires further substantiation. We investigated the effect of pulmonary delivery of nanoparticle (NP)-conjugated CpG on lung immunity and found that NP-CpG led to enhanced recruitment of activated dendritic cells and to Th1 immunity compared to free CpG. We then evaluated if pulmonary delivery of NP-CpG could prevent and treat house dust mite-induced allergy by modulating immunity directly in lungs. When CpG was administered as immunomodulatory therapy prior to allergen sensitization, we found that NP-CpG significantly reduced eosinophilia, IgE levels, mucus production and Th2 cytokines, while free CpG had only a moderate effect on these parameters. In a therapeutic setting where CpG was administered after allergen sensitization, we found that although both free CpG and NP-CpG reduced eosinophilia and IgE levels to the same extent, NP conjugation of CpG significantly enhanced reduction of Th2 cytokines in lungs of allergic mice. Taken together, these data highlight benefits of NP conjugation and the relevance of NP-CpG as allergen-free therapy to modulate lung immunity and treat airway allergy.
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spelling pubmed-45857082015-09-29 Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice Ballester, Marie Jeanbart, Laura de Titta, Alexandre Nembrini, Chiara Marsland, Benjamin J. Hubbell, Jeffrey A. Swartz, Melody A. Sci Rep Article An emerging strategy in preventing and treating airway allergy consists of modulating the immune response induced against allergens in the lungs. CpG oligodeoxynucleotides have been investigated in airway allergy studies, but even if promising, efficacy requires further substantiation. We investigated the effect of pulmonary delivery of nanoparticle (NP)-conjugated CpG on lung immunity and found that NP-CpG led to enhanced recruitment of activated dendritic cells and to Th1 immunity compared to free CpG. We then evaluated if pulmonary delivery of NP-CpG could prevent and treat house dust mite-induced allergy by modulating immunity directly in lungs. When CpG was administered as immunomodulatory therapy prior to allergen sensitization, we found that NP-CpG significantly reduced eosinophilia, IgE levels, mucus production and Th2 cytokines, while free CpG had only a moderate effect on these parameters. In a therapeutic setting where CpG was administered after allergen sensitization, we found that although both free CpG and NP-CpG reduced eosinophilia and IgE levels to the same extent, NP conjugation of CpG significantly enhanced reduction of Th2 cytokines in lungs of allergic mice. Taken together, these data highlight benefits of NP conjugation and the relevance of NP-CpG as allergen-free therapy to modulate lung immunity and treat airway allergy. Nature Publishing Group 2015-09-21 /pmc/articles/PMC4585708/ /pubmed/26387548 http://dx.doi.org/10.1038/srep14274 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Ballester, Marie
Jeanbart, Laura
de Titta, Alexandre
Nembrini, Chiara
Marsland, Benjamin J.
Hubbell, Jeffrey A.
Swartz, Melody A.
Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice
title Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice
title_full Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice
title_fullStr Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice
title_full_unstemmed Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice
title_short Nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered CpG in house dust mite-allergic mice
title_sort nanoparticle conjugation enhances the immunomodulatory effects of intranasally delivered cpg in house dust mite-allergic mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585708/
https://www.ncbi.nlm.nih.gov/pubmed/26387548
http://dx.doi.org/10.1038/srep14274
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