NLRP3 inflammasome-activating arginine-based liposomes promote antigen presentations in dendritic cells

Tianshu Li,1 Matthias Zehner,2 Jieyan He,3 Tomasz Próchnicki,4 Gabor Horvath,4 Eicke Latz,4 Sven Burgdorf,2 Shinji Takeoka1,31Institute for Advanced Research of Biosystem Dynamics, Waseda Research Institute for Science and Engineering, Waseda University, Tokyo, Japan; 2Molecular Immunolog...

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Autores principales:	Li T, Zehner M, He J, Próchnicki T, Horvath G, Latz E, Burgdorf S, Takeoka S
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	arginine cationic liposomes NLRP3 inflammasome activation antigen presentation lysosome rupture Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/c63fa176106c4e0ea49f4e342f5aede0
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spelling	oai:doaj.org-article:c63fa176106c4e0ea49f4e342f5aede02021-12-02T05:28:19ZNLRP3 inflammasome-activating arginine-based liposomes promote antigen presentations in dendritic cells1178-2013https://doaj.org/article/c63fa176106c4e0ea49f4e342f5aede02019-05-01T00:00:00Zhttps://www.dovepress.com/nlrp3-inflammasome-activating-arginine-based-liposomes-promote-antigen-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Tianshu Li,1 Matthias Zehner,2 Jieyan He,3 Tomasz Próchnicki,4 Gabor Horvath,4 Eicke Latz,4 Sven Burgdorf,2 Shinji Takeoka1,31Institute for Advanced Research of Biosystem Dynamics, Waseda Research Institute for Science and Engineering, Waseda University, Tokyo, Japan; 2Molecular Immunology and Cell Biology, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany; 3Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan; 4Institute of Innate Immunity, Biomedical Center, University Hospitals, University of Bonn, Bonn, GermanyPurpose: The NLRP3 inflammasome activation has been proposed as a common mechanism for some adjuvants to boost the immune system, and cationic liposomes were reported to potentially activate the NLRP3 inflammasome. Herein, we questioned whether the NLRP3 inflammasome-activating cationic liposomes could promote antigen presentation and be applied as an immune adjuvant. In addition, we aimed to investigate the structure effect of lipid on triggering these immune responses.Materials and methods: A series of structurally similar lipids, consisting of arginine (Arg) head group and varied lengths of alkyl chains or spacers in between were used to prepare cationic liposomes. Lipopolysaccharide-primed human or murine macrophages or phorbol 12-myristate 13-acetate-primed THP-1 cells were treated with these liposomes, and interleukin (IL)-1β secretion was measured to quantify the NLRP3 inflammasome activation. Lysosome rupture was examined in THP-1 cells by the fluorescence loss of acridine orange, a lysosome dye. Further, chicken ovalbumin (OVA) was loaded on the liposome surface and applied to murine bone marrow-derived dendritic cells (BMDCs), which activate OT-I and OT-II lymphocytes upon major histocompatibility complex (MHC) class I- and class II-mediated antigen presentation, respectively. OT-I and OT-II cell division and IL-2 secretion were measured to evaluate the antigen presentation efficiency. The expressions of MHC molecules and co-stimulatory molecules ie, CD80, CD86, and CD40 on BMDCs were investigated by flow cytometry.Results: All the liposomes showed size distributions of 80–200 nm and zeta potentials of around 50 mV. A3C14 liposomes, consisting of Arg-C3-Glu2C14 lipids induced the most potent lysosome rupture and NLRP3 inflammasome activation. OVA-A3C14 also exhibited the most potent MHC class I- and class II-mediated antigen presentation in BMDCs without interfering MHC and co-stimulatory molecules.Conclusion: The hydrophobic moieties of arginine-based liposomes are crucial in stimulating innate immune cells. A3C14 liposomes were non-immunogenic but strongly activated innate immune cells and promoted antigen presentation, and therefore can be applied as immune adjuvants.Keywords: arginine, cationic liposomes, NLRP3 inflammasome activation, antigen presentation, lysosome ruptureLi TZehner MHe JPróchnicki THorvath GLatz EBurgdorf STakeoka SDove Medical Pressarticleargininecationic liposomesNLRP3 inflammasome activationantigen presentationlysosome ruptureMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 3503-3516 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	arginine cationic liposomes NLRP3 inflammasome activation antigen presentation lysosome rupture Medicine (General) R5-920
spellingShingle	arginine cationic liposomes NLRP3 inflammasome activation antigen presentation lysosome rupture Medicine (General) R5-920 Li T Zehner M He J Próchnicki T Horvath G Latz E Burgdorf S Takeoka S NLRP3 inflammasome-activating arginine-based liposomes promote antigen presentations in dendritic cells
description	Tianshu Li,1 Matthias Zehner,2 Jieyan He,3 Tomasz Próchnicki,4 Gabor Horvath,4 Eicke Latz,4 Sven Burgdorf,2 Shinji Takeoka1,31Institute for Advanced Research of Biosystem Dynamics, Waseda Research Institute for Science and Engineering, Waseda University, Tokyo, Japan; 2Molecular Immunology and Cell Biology, Life and Medical Sciences Institute, University of Bonn, Bonn, Germany; 3Department of Life Science and Medical Bioscience, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan; 4Institute of Innate Immunity, Biomedical Center, University Hospitals, University of Bonn, Bonn, GermanyPurpose: The NLRP3 inflammasome activation has been proposed as a common mechanism for some adjuvants to boost the immune system, and cationic liposomes were reported to potentially activate the NLRP3 inflammasome. Herein, we questioned whether the NLRP3 inflammasome-activating cationic liposomes could promote antigen presentation and be applied as an immune adjuvant. In addition, we aimed to investigate the structure effect of lipid on triggering these immune responses.Materials and methods: A series of structurally similar lipids, consisting of arginine (Arg) head group and varied lengths of alkyl chains or spacers in between were used to prepare cationic liposomes. Lipopolysaccharide-primed human or murine macrophages or phorbol 12-myristate 13-acetate-primed THP-1 cells were treated with these liposomes, and interleukin (IL)-1β secretion was measured to quantify the NLRP3 inflammasome activation. Lysosome rupture was examined in THP-1 cells by the fluorescence loss of acridine orange, a lysosome dye. Further, chicken ovalbumin (OVA) was loaded on the liposome surface and applied to murine bone marrow-derived dendritic cells (BMDCs), which activate OT-I and OT-II lymphocytes upon major histocompatibility complex (MHC) class I- and class II-mediated antigen presentation, respectively. OT-I and OT-II cell division and IL-2 secretion were measured to evaluate the antigen presentation efficiency. The expressions of MHC molecules and co-stimulatory molecules ie, CD80, CD86, and CD40 on BMDCs were investigated by flow cytometry.Results: All the liposomes showed size distributions of 80–200 nm and zeta potentials of around 50 mV. A3C14 liposomes, consisting of Arg-C3-Glu2C14 lipids induced the most potent lysosome rupture and NLRP3 inflammasome activation. OVA-A3C14 also exhibited the most potent MHC class I- and class II-mediated antigen presentation in BMDCs without interfering MHC and co-stimulatory molecules.Conclusion: The hydrophobic moieties of arginine-based liposomes are crucial in stimulating innate immune cells. A3C14 liposomes were non-immunogenic but strongly activated innate immune cells and promoted antigen presentation, and therefore can be applied as immune adjuvants.Keywords: arginine, cationic liposomes, NLRP3 inflammasome activation, antigen presentation, lysosome rupture
format	article
author	Li T Zehner M He J Próchnicki T Horvath G Latz E Burgdorf S Takeoka S
author_facet	Li T Zehner M He J Próchnicki T Horvath G Latz E Burgdorf S Takeoka S
author_sort	Li T
title	NLRP3 inflammasome-activating arginine-based liposomes promote antigen presentations in dendritic cells
title_short	NLRP3 inflammasome-activating arginine-based liposomes promote antigen presentations in dendritic cells
title_full	NLRP3 inflammasome-activating arginine-based liposomes promote antigen presentations in dendritic cells
title_fullStr	NLRP3 inflammasome-activating arginine-based liposomes promote antigen presentations in dendritic cells
title_full_unstemmed	NLRP3 inflammasome-activating arginine-based liposomes promote antigen presentations in dendritic cells
title_sort	nlrp3 inflammasome-activating arginine-based liposomes promote antigen presentations in dendritic cells
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/c63fa176106c4e0ea49f4e342f5aede0
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NLRP3 inflammasome-activating arginine-based liposomes promote antigen presentations in dendritic cells

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