Journal ArticleDOI
DNA released from dying host cells mediates aluminum adjuvant activity
Thomas Marichal,Keiichi Ohata,Denis Bedoret,Claire Mesnil,Catherine Sabatel,Kouji Kobiyama,Pierre Lekeux,Cevayir Coban,Shizuo Akira,Ken Ishii,Fabrice Bureau,Christophe Desmet +11 more
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TLDR
The finding that host DNA released from dying cells acts as a damage-associated molecular pattern that mediates alum adjuvant activity may increase the understanding of the mechanisms of action of current vaccines and help in the design of new adjuvants.Abstract:
Aluminum-based adjuvants (aluminum salts or alum) are widely used in human vaccination, although their mechanisms of action are poorly understood. Here we report that, in mice, alum causes cell death and the subsequent release of host cell DNA, which acts as a potent endogenous immunostimulatory signal mediating alum adjuvant activity. Furthermore, we propose that host DNA signaling differentially regulates IgE and IgG1 production after alum-adjuvanted immunization. We suggest that, on the one hand, host DNA induces primary B cell responses, including IgG1 production, through interferon response factor 3 (Irf3)-independent mechanisms. On the other hand, we suggest that host DNA also stimulates 'canonical' T helper type 2 (T H 2) responses, associated with IgE isotype switching and peripheral effector responses, through Irf3-dependent mechanisms. The finding that host DNA released from dying cells acts as a damage-associated molecular pattern that mediates alum adjuvant activity may increase our understanding of the mechanisms of action of current vaccines and help in the design of new adjuvants.read more
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Q969R polymorphism in NLRP3 is associated with immune responses to vaccination against bacterial infections in pigs
TL;DR: A significant association of the antibody response against Haemophilus parasuis serotype 2 and 5 with NLRP3 genotypes is observed and there is potential for improvement in vaccine efficiency and disease resistance using this polymorphism in various pig populations.
Journal ArticleDOI
Caspase-1-Dependent Pyroptosis Mediates Adjuvant Activity of Platycodin D as an Adjuvant for Intramuscular Vaccines
TL;DR: Findings identified the caspase-1-dependent adjuvanticity of PD and expanded the current knowledge on the mechanisms of action of saponin-based adjuvants.
Journal ArticleDOI
Understanding Host Immunity and the Gut Microbiota Inspires the New Development of Vaccines and Adjuvants.
TL;DR: How the gut microbiota influences immunity and the relationship between gut microbes and trained innate immunity, vaccines, and adjuvants is discussed and Understanding these complex interactions will provide insights into novel vaccine approaches centered on the Gut microbiota.
Journal ArticleDOI
A recombinant multi-epitope protein MEP1 elicits efficient long-term immune responses against HIV-1 infection.
Yi Yang,Qing Zhu,Weilai Sun,Jingjing Guo,Xiuzhe Ning,Qiao Li,Yan Guo,Junfeng Li,Zhihua Kou,Yusen Zhou +9 more
TL;DR: MEP1 has the potential to be developed as an effective vaccine candidate, and it is suggested that suitable adjuvant is necessary for this protein to generate protective immune responses.
References
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Osamu Takeuchi,Shizuo Akira +1 more
TL;DR: The role of PRRs, their signaling pathways, and how they control inflammatory responses are discussed.
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Hiroaki Hemmi,Osamu Takeuchi,Taro Kawai,Tsuneyasu Kaisho,Shintaro Sato,Hideki Sanjo,Makoto Matsumoto,Katsuaki Hoshino,Hermann Wagner,Kiyoshi Takeda,Shizuo Akira +10 more
TL;DR: It is shown that cellular response to CpG DNA is mediated by a Toll-like receptor, TLR9, and vertebrate immune systems appear to have evolved a specific Toll- like receptor that distinguishes bacterial DNA from self-DNA.
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Cryopyrin activates the inflammasome in response to toxins and ATP
Sanjeev Mariathasan,David S. Weiss,Kim Newton,Jacqueline McBride,Karen O'Rourke,Meron Roose-Girma,Wyne P. Lee,Yvette Weinrauch,Denise M. Monack,Vishva M. Dixit +9 more
TL;DR: It is shown that cryopyrin-deficient macrophages cannot activate caspase-1 in response to Toll-like receptor agonists plus ATP, the latter activating the P2X7 receptor to decrease intracellular K+ levels.
Journal ArticleDOI
Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization
Veit Hornung,Franz Bauernfeind,Annett Halle,Eivind O. Samstad,Eivind O. Samstad,Hajime Kono,Kenneth L. Rock,Katherine A. Fitzgerald,Eicke Latz,Eicke Latz +9 more
TL;DR: It is demonstrated that silica and aluminum salt crystals activated inflammasomes formed by the cytoplasmic receptor NALP3, which senses lysosomal damage as an endogenous 'danger' signal.
Journal ArticleDOI
Sterile inflammation: sensing and reacting to damage
Grace Y. Chen,Gabriel Núñez +1 more
TL;DR: The triggers and receptor pathways that result in sterile inflammation and its impact on human health are reviewed.