Cationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal pH and limiting the degradation of antigens

Jie Gao,1–3 Lukasz J Ochyl,1,3 Ellen Yang,4 James J Moon1,3,5 1Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA; 2Department of Pharmaceutical Sciences, School of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of China;...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Gao J, Ochyl LJ, Yang E, Moon JJ
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2017
Materias:	cationic liposome nanoparticle vaccine cross-presentation lysosome Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/4770b51d056c4ae1982baf360e7fc0b0
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:4770b51d056c4ae1982baf360e7fc0b0
record_format	dspace
spelling	oai:doaj.org-article:4770b51d056c4ae1982baf360e7fc0b02021-12-02T05:10:27ZCationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal pH and limiting the degradation of antigens1178-2013https://doaj.org/article/4770b51d056c4ae1982baf360e7fc0b02017-02-01T00:00:00Zhttps://www.dovepress.com/cationic-liposomes-promote-antigen-cross-presentation-in-dendritic-cel-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Jie Gao,1–3 Lukasz J Ochyl,1,3 Ellen Yang,4 James J Moon1,3,5 1Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA; 2Department of Pharmaceutical Sciences, School of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of China; 3Biointerfaces Institute, 4Department of Chemistry, 5Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA Abstract: Cationic liposomes (CLs) have been widely examined as vaccine delivery nanoparticles since they can form complexes with biomacromolecules, promote delivery of antigens and adjuvant molecules to antigen-presenting cells (APCs), and mediate cellular uptake of vaccine components. CLs are also known to trigger antigen cross-presentation – the process by which APCs internalize extracellular protein antigens, degrade them into minimal CD8+ T-cell epitopes, and present them in the context of major histocompatibility complex-I (MHC-I). However, the precise mechanisms behind CL-mediated induction of cross-presentation and cross-priming of CD8+ T-cells remain to be elucidated. In this study, we have developed two distinct CL systems and examined their impact on the lysosomal pH in dendritic cells (DCs), antigen degradation, and presentation of peptide:MHC-I complexes to antigen-specific CD8+ T-cells. To achieve this, we have used 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as the prototypical components of CLs with tertiary amine groups and compared the effect of CLs and anionic liposomes on lysosomal pH, antigen degradation, and cross-presentation by DCs. Our results showed that CLs, but not anionic liposomes, elevated the lysosomal pH in DCs and reduced antigen degradation, thereby promoting cross-presentation and cross-priming of CD8+ T-cell responses. These studies shed new light on CL-mediated cross-presentation and suggest that intracellular fate of vaccine components and subsequent immunological responses can be controlled by rational design of nanomaterials. Keywords: cationic liposome, nanoparticle, vaccine, cross-presentation, lysosomeGao JOchyl LJYang EMoon JJDove Medical Pressarticlecationic liposomenanoparticlevaccinecross-presentationlysosomeMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 12, Pp 1251-1264 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	cationic liposome nanoparticle vaccine cross-presentation lysosome Medicine (General) R5-920
spellingShingle	cationic liposome nanoparticle vaccine cross-presentation lysosome Medicine (General) R5-920 Gao J Ochyl LJ Yang E Moon JJ Cationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal pH and limiting the degradation of antigens
description	Jie Gao,1–3 Lukasz J Ochyl,1,3 Ellen Yang,4 James J Moon1,3,5 1Department of Pharmaceutical Sciences, University of Michigan, Ann Arbor, MI, USA; 2Department of Pharmaceutical Sciences, School of Pharmacy, Second Military Medical University, Shanghai, People’s Republic of China; 3Biointerfaces Institute, 4Department of Chemistry, 5Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA Abstract: Cationic liposomes (CLs) have been widely examined as vaccine delivery nanoparticles since they can form complexes with biomacromolecules, promote delivery of antigens and adjuvant molecules to antigen-presenting cells (APCs), and mediate cellular uptake of vaccine components. CLs are also known to trigger antigen cross-presentation – the process by which APCs internalize extracellular protein antigens, degrade them into minimal CD8+ T-cell epitopes, and present them in the context of major histocompatibility complex-I (MHC-I). However, the precise mechanisms behind CL-mediated induction of cross-presentation and cross-priming of CD8+ T-cells remain to be elucidated. In this study, we have developed two distinct CL systems and examined their impact on the lysosomal pH in dendritic cells (DCs), antigen degradation, and presentation of peptide:MHC-I complexes to antigen-specific CD8+ T-cells. To achieve this, we have used 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-Chol) and 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) as the prototypical components of CLs with tertiary amine groups and compared the effect of CLs and anionic liposomes on lysosomal pH, antigen degradation, and cross-presentation by DCs. Our results showed that CLs, but not anionic liposomes, elevated the lysosomal pH in DCs and reduced antigen degradation, thereby promoting cross-presentation and cross-priming of CD8+ T-cell responses. These studies shed new light on CL-mediated cross-presentation and suggest that intracellular fate of vaccine components and subsequent immunological responses can be controlled by rational design of nanomaterials. Keywords: cationic liposome, nanoparticle, vaccine, cross-presentation, lysosome
format	article
author	Gao J Ochyl LJ Yang E Moon JJ
author_facet	Gao J Ochyl LJ Yang E Moon JJ
author_sort	Gao J
title	Cationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal pH and limiting the degradation of antigens
title_short	Cationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal pH and limiting the degradation of antigens
title_full	Cationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal pH and limiting the degradation of antigens
title_fullStr	Cationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal pH and limiting the degradation of antigens
title_full_unstemmed	Cationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal pH and limiting the degradation of antigens
title_sort	cationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal ph and limiting the degradation of antigens
publisher	Dove Medical Press
publishDate	2017
url	https://doaj.org/article/4770b51d056c4ae1982baf360e7fc0b0
work_keys_str_mv	AT gaoj cationicliposomespromoteantigencrosspresentationindendriticcellsbyalkalizingthelysosomalphandlimitingthedegradationofantigens AT ochyllj cationicliposomespromoteantigencrosspresentationindendriticcellsbyalkalizingthelysosomalphandlimitingthedegradationofantigens AT yange cationicliposomespromoteantigencrosspresentationindendriticcellsbyalkalizingthelysosomalphandlimitingthedegradationofantigens AT moonjj cationicliposomespromoteantigencrosspresentationindendriticcellsbyalkalizingthelysosomalphandlimitingthedegradationofantigens
_version_	1718400526627897344

Cationic liposomes promote antigen cross-presentation in dendritic cells by alkalizing the lysosomal pH and limiting the degradation of antigens

Ejemplares similares