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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| Format: | Article |
| Language: | English |
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MDPI AG
2019-12-01
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| Series: | Vaccines |
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| Online Access: | https://www.mdpi.com/2076-393X/8/1/8 |
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| author | Rui Tada Akihiro Ohshima Yuya Tanazawa Akari Ohmi Saeko Takahashi Hiroshi Kiyono Jun Kunisawa Yukihiko Aramaki Yoichi Negishi |
| author_facet | Rui Tada Akihiro Ohshima Yuya Tanazawa Akari Ohmi Saeko Takahashi Hiroshi Kiyono Jun Kunisawa Yukihiko Aramaki Yoichi Negishi |
| author_sort | Rui Tada |
| collection | DOAJ |
| 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, <i>in vivo</i> 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. |
| first_indexed | 2024-04-13T00:46:17Z |
| format | Article |
| id | doaj.art-1b0cb1e8ddf740e9b5e02682c5c78cb2 |
| institution | Directory Open Access Journal |
| issn | 2076-393X |
| language | English |
| last_indexed | 2024-04-13T00:46:17Z |
| publishDate | 2019-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Vaccines |
| spelling | doaj.art-1b0cb1e8ddf740e9b5e02682c5c78cb22022-12-22T03:10:00ZengMDPI AGVaccines2076-393X2019-12-0181810.3390/vaccines8010008vaccines8010008Essential Role of Host Double-Stranded DNA Released from Dying Cells by Cationic Liposomes for Mucosal AdjuvanticityRui Tada0Akihiro Ohshima1Yuya Tanazawa2Akari Ohmi3Saeko Takahashi4Hiroshi Kiyono5Jun Kunisawa6Yukihiko Aramaki7Yoichi Negishi8Department of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanDepartment of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanDepartment of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanDepartment of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanDepartment of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanDivision of Mucosal Immunology and International Research and Development Center for Mucosal Vaccines, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, JapanDivision of Mucosal Immunology and International Research and Development Center for Mucosal Vaccines, Department of Microbiology and Immunology, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, JapanDepartment of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanDepartment of Drug Delivery and Molecular Biopharmaceutics, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences, Tokyo 192-0392, JapanInfectious 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, <i>in vivo</i> 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.https://www.mdpi.com/2076-393X/8/1/8cationic liposomedampsdsdnadying cellsmucosal adjuvant |
| spellingShingle | Rui Tada Akihiro Ohshima Yuya Tanazawa Akari Ohmi Saeko Takahashi Hiroshi Kiyono Jun Kunisawa Yukihiko Aramaki Yoichi Negishi Essential Role of Host Double-Stranded DNA Released from Dying Cells by Cationic Liposomes for Mucosal Adjuvanticity Vaccines cationic liposome damps dsdna dying cells mucosal adjuvant |
| 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 | cationic liposome damps dsdna dying cells mucosal adjuvant |
| url | https://www.mdpi.com/2076-393X/8/1/8 |
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