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Essential Role of Host Double-Stranded DNA Released from Dying Cells by Cationic Liposomes for Mucosal Adjuvanticity

Infectious disease remains a substantial cause of death. To overcome this issue, mucosal vaccine systems are considered to be a promising strategy. Yet, none are approved for clinical use, except for live-attenuated mucosal vaccines, mainly owing to the lack of effective and safe systems to induce a...

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Autores principales: Tada, Rui, Ohshima, Akihiro, Tanazawa, Yuya, Ohmi, Akari, Takahashi, Saeko, Kiyono, Hiroshi, Kunisawa, Jun, Aramaki, Yukihiko, Negishi, Yoichi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157664/
https://www.ncbi.nlm.nih.gov/pubmed/31892192
http://dx.doi.org/10.3390/vaccines8010008
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author Tada, Rui
Ohshima, Akihiro
Tanazawa, Yuya
Ohmi, Akari
Takahashi, Saeko
Kiyono, Hiroshi
Kunisawa, Jun
Aramaki, Yukihiko
Negishi, Yoichi
author_facet Tada, Rui
Ohshima, Akihiro
Tanazawa, Yuya
Ohmi, Akari
Takahashi, Saeko
Kiyono, Hiroshi
Kunisawa, Jun
Aramaki, Yukihiko
Negishi, Yoichi
author_sort Tada, Rui
collection PubMed
description Infectious disease remains a substantial cause of death. To overcome this issue, mucosal vaccine systems are considered to be a promising strategy. Yet, none are approved for clinical use, except for live-attenuated mucosal vaccines, mainly owing to the lack of effective and safe systems to induce antigen-specific immune responses in the mucosal compartment. We have reported that intranasal vaccination of an antigenic protein, with cationic liposomes composed of 1,2-dioleoyl-3-trimethylammonium-propane and 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl], induced antigen-specific mucosal and systemic antibody responses in mice. However, precise molecular mechanism(s) underlying the mucosal adjuvant effects of cationic liposomes remain to be uncovered. Here, we show that a host double-stranded DNA (dsDNA), released at the site of cationic liposome injection, plays an essential role for the mucosal adjuvanticity of the cationic liposome. Namely, we found that nasal administration of the cationic liposomes induced localized cell death, at the site of injection, resulting in extracellular leakage of host dsDNA. Additionally, in vivo DNase I treatment markedly impaired OVA-specific mucosal and systemic antibody production exerted by cationic liposomes. Our report reveals that host dsDNA, released from local dying cells, acts as a damage-associated molecular pattern that mediates the mucosal adjuvant activity of cationic liposomes.
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spelling pubmed-71576642020-05-01 Essential Role of Host Double-Stranded DNA Released from Dying Cells by Cationic Liposomes for Mucosal Adjuvanticity Tada, Rui Ohshima, Akihiro Tanazawa, Yuya Ohmi, Akari Takahashi, Saeko Kiyono, Hiroshi Kunisawa, Jun Aramaki, Yukihiko Negishi, Yoichi Vaccines (Basel) Article Infectious disease remains a substantial cause of death. To overcome this issue, mucosal vaccine systems are considered to be a promising strategy. Yet, none are approved for clinical use, except for live-attenuated mucosal vaccines, mainly owing to the lack of effective and safe systems to induce antigen-specific immune responses in the mucosal compartment. We have reported that intranasal vaccination of an antigenic protein, with cationic liposomes composed of 1,2-dioleoyl-3-trimethylammonium-propane and 3β-[N-(N′,N′-dimethylaminoethane)-carbamoyl], induced antigen-specific mucosal and systemic antibody responses in mice. However, precise molecular mechanism(s) underlying the mucosal adjuvant effects of cationic liposomes remain to be uncovered. Here, we show that a host double-stranded DNA (dsDNA), released at the site of cationic liposome injection, plays an essential role for the mucosal adjuvanticity of the cationic liposome. Namely, we found that nasal administration of the cationic liposomes induced localized cell death, at the site of injection, resulting in extracellular leakage of host dsDNA. Additionally, in vivo DNase I treatment markedly impaired OVA-specific mucosal and systemic antibody production exerted by cationic liposomes. Our report reveals that host dsDNA, released from local dying cells, acts as a damage-associated molecular pattern that mediates the mucosal adjuvant activity of cationic liposomes. MDPI 2019-12-27 /pmc/articles/PMC7157664/ /pubmed/31892192 http://dx.doi.org/10.3390/vaccines8010008 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tada, Rui
Ohshima, Akihiro
Tanazawa, Yuya
Ohmi, Akari
Takahashi, Saeko
Kiyono, Hiroshi
Kunisawa, Jun
Aramaki, Yukihiko
Negishi, Yoichi
Essential Role of Host Double-Stranded DNA Released from Dying Cells by Cationic Liposomes for Mucosal Adjuvanticity
title Essential Role of Host Double-Stranded DNA Released from Dying Cells by Cationic Liposomes for Mucosal Adjuvanticity
title_full Essential Role of Host Double-Stranded DNA Released from Dying Cells by Cationic Liposomes for Mucosal Adjuvanticity
title_fullStr Essential Role of Host Double-Stranded DNA Released from Dying Cells by Cationic Liposomes for Mucosal Adjuvanticity
title_full_unstemmed Essential Role of Host Double-Stranded DNA Released from Dying Cells by Cationic Liposomes for Mucosal Adjuvanticity
title_short Essential Role of Host Double-Stranded DNA Released from Dying Cells by Cationic Liposomes for Mucosal Adjuvanticity
title_sort essential role of host double-stranded dna released from dying cells by cationic liposomes for mucosal adjuvanticity
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7157664/
https://www.ncbi.nlm.nih.gov/pubmed/31892192
http://dx.doi.org/10.3390/vaccines8010008
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