Journal
VACCINES
Volume 8, Issue 1, Pages -Publisher
MDPI
DOI: 10.3390/vaccines8010008
Keywords
cationic liposome; DAMPs; dsDNA; dying cells; mucosal adjuvant
Categories
Funding
- JSPS KAKENHI [15K18935, 18K06798, 16K08415]
- Japan Agency for Medical Research and Development [18ak0101068h0002]
- Science Research Promotion Fund from the Promotion and Mutual Aid Corporation for Private Schools of Japan
- Grants-in-Aid for Scientific Research [18K06798, 15K18935, 16K08415] Funding Source: KAKEN
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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 3 beta-[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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