Size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation

Emilie Seydoux,1,2 Barbara Rothen-Rutishauser,1,3 Izabela M Nita,1 Sandor Balog,3 Amiq Gazdhar,1 Philip A Stumbles,4,5 Alke Petri-Fink,3,6 Fabian Blank,1,* Christophe von Garnier1,*1Department of Respiratory Medicine, Inselspit...

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Autores principales:	Seydoux E, Rothen-Rutishauser B, Nita IM, Balog S, Gazdhar A, Stumbles PA, Petri-Fink A, Blank F, von Garnier C
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2014
Materias:	Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/877fdef764f34ee191732e10d68b14b6
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spelling	oai:doaj.org-article:877fdef764f34ee191732e10d68b14b62021-12-02T07:46:14ZSize-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation1178-2013https://doaj.org/article/877fdef764f34ee191732e10d68b14b62014-08-01T00:00:00Zhttp://www.dovepress.com/size-dependent-accumulation-of-particles-in-lysosomes-modulates-dendri-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013 Emilie Seydoux,1,2 Barbara Rothen-Rutishauser,1,3 Izabela M Nita,1 Sandor Balog,3 Amiq Gazdhar,1 Philip A Stumbles,4,5 Alke Petri-Fink,3,6 Fabian Blank,1,* Christophe von Garnier1,1Department of Respiratory Medicine, Inselspital, Bern University Hospital, Department of Clinical Research, University of Bern, 2Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland; 3Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland; 4School of Veterinary and Life Sciences, Molecular and Biomedical Sciences, Murdoch University, Perth, WA, Australia; 5Telethon Kids Institute, Perth, WA, Australia; 6Department of Chemistry, University of Fribourg, Fribourg, SwitzerlandThese authors contributed equally to the manuscriptIntroduction: Nanosized particles may enable therapeutic modulation of immune responses by targeting dendritic cell (DC) networks in accessible organs such as the lung. To date, however, the effects of nanoparticles on DC function and downstream immune responses remain poorly understood. Methods: Bone marrow–derived DCs (BMDCs) were exposed in vitro to 20 or 1,000 nm polystyrene (PS) particles. Particle uptake kinetics, cell surface marker expression, soluble protein antigen uptake and degradation, as well as in vitro CD4+ T-cell proliferation and cytokine production were analyzed by flow cytometry. In addition, co-localization of particles within the lysosomal compartment, lysosomal permeability, and endoplasmic reticulum stress were analyzed. Results: The frequency of PS particle–positive CD11c+/CD11b+ BMDCs reached an early plateau after 20 minutes and was significantly higher for 20 nm than for 1,000 nm PS particles at all time-points analyzed. PS particles did not alter cell viability or modify expression of the surface markers CD11b, CD11c, MHC class II, CD40, and CD86. Although particle exposure did not modulate antigen uptake, 20 nm PS particles decreased the capacity of BMDCs to degrade soluble antigen, without affecting their ability to induce antigen-specific CD4+ T-cell proliferation. Co-localization studies between PS particles and lysosomes using laser scanning confocal microscopy detected a significantly higher frequency of co-localized 20 nm particles as compared with their 1,000 nm counterparts. Neither size of PS particle caused lysosomal leakage, expression of endoplasmic reticulum stress gene markers, or changes in cytokines profiles. Conclusion: These data indicate that although supposedly inert PS nanoparticles did not induce DC activation or alteration in CD4+ T-cell stimulating capacity, 20 nm (but not 1,000 nm) PS particles may reduce antigen degradation through interference in the lysosomal compartment. These findings emphasize the importance of performing in-depth analysis of DC function when developing novel approaches for immune modulation with nanoparticles. Keywords: polystyrene particles, nanoparticles, immune modulation, mouse dendritic cells, CD4+ T-cellsSeydoux ERothen-Rutishauser BNita IMBalog SGazdhar AStumbles PAPetri-Fink ABlank Fvon Garnier CDove Medical PressarticleMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol 2014, Iss Issue 1, Pp 3885-3902 (2014)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine (General) R5-920
spellingShingle	Medicine (General) R5-920 Seydoux E Rothen-Rutishauser B Nita IM Balog S Gazdhar A Stumbles PA Petri-Fink A Blank F von Garnier C Size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation
description	Emilie Seydoux,1,2 Barbara Rothen-Rutishauser,1,3 Izabela M Nita,1 Sandor Balog,3 Amiq Gazdhar,1 Philip A Stumbles,4,5 Alke Petri-Fink,3,6 Fabian Blank,1,* Christophe von Garnier1,1Department of Respiratory Medicine, Inselspital, Bern University Hospital, Department of Clinical Research, University of Bern, 2Graduate School for Cellular and Biomedical Sciences, University of Bern, Bern, Switzerland; 3Adolphe Merkle Institute, University of Fribourg, Fribourg, Switzerland; 4School of Veterinary and Life Sciences, Molecular and Biomedical Sciences, Murdoch University, Perth, WA, Australia; 5Telethon Kids Institute, Perth, WA, Australia; 6Department of Chemistry, University of Fribourg, Fribourg, SwitzerlandThese authors contributed equally to the manuscriptIntroduction: Nanosized particles may enable therapeutic modulation of immune responses by targeting dendritic cell (DC) networks in accessible organs such as the lung. To date, however, the effects of nanoparticles on DC function and downstream immune responses remain poorly understood. Methods: Bone marrow–derived DCs (BMDCs) were exposed in vitro to 20 or 1,000 nm polystyrene (PS) particles. Particle uptake kinetics, cell surface marker expression, soluble protein antigen uptake and degradation, as well as in vitro CD4+ T-cell proliferation and cytokine production were analyzed by flow cytometry. In addition, co-localization of particles within the lysosomal compartment, lysosomal permeability, and endoplasmic reticulum stress were analyzed. Results: The frequency of PS particle–positive CD11c+/CD11b+ BMDCs reached an early plateau after 20 minutes and was significantly higher for 20 nm than for 1,000 nm PS particles at all time-points analyzed. PS particles did not alter cell viability or modify expression of the surface markers CD11b, CD11c, MHC class II, CD40, and CD86. Although particle exposure did not modulate antigen uptake, 20 nm PS particles decreased the capacity of BMDCs to degrade soluble antigen, without affecting their ability to induce antigen-specific CD4+ T-cell proliferation. Co-localization studies between PS particles and lysosomes using laser scanning confocal microscopy detected a significantly higher frequency of co-localized 20 nm particles as compared with their 1,000 nm counterparts. Neither size of PS particle caused lysosomal leakage, expression of endoplasmic reticulum stress gene markers, or changes in cytokines profiles. Conclusion: These data indicate that although supposedly inert PS nanoparticles did not induce DC activation or alteration in CD4+ T-cell stimulating capacity, 20 nm (but not 1,000 nm) PS particles may reduce antigen degradation through interference in the lysosomal compartment. These findings emphasize the importance of performing in-depth analysis of DC function when developing novel approaches for immune modulation with nanoparticles. Keywords: polystyrene particles, nanoparticles, immune modulation, mouse dendritic cells, CD4+ T-cells
format	article
author	Seydoux E Rothen-Rutishauser B Nita IM Balog S Gazdhar A Stumbles PA Petri-Fink A Blank F von Garnier C
author_facet	Seydoux E Rothen-Rutishauser B Nita IM Balog S Gazdhar A Stumbles PA Petri-Fink A Blank F von Garnier C
author_sort	Seydoux E
title	Size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation
title_short	Size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation
title_full	Size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation
title_fullStr	Size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation
title_full_unstemmed	Size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation
title_sort	size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation
publisher	Dove Medical Press
publishDate	2014
url	https://doaj.org/article/877fdef764f34ee191732e10d68b14b6
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Size-dependent accumulation of particles in lysosomes modulates dendritic cell function through impaired antigen degradation

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