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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Adjuvant for vaccine immunotherapy of cancer--focusing on Toll-like receptor 2 and 3 agonists for safely enhancing antitumor immunity.
TL;DR: The history and perspectives of TLR2 and TLR3 agonists in vaccine‐adjuvant immunotherapy for cancer are summarized.
Journal ArticleDOI
Unraveling the enigma: elucidating the relationship between the physicochemical properties of aluminium-based adjuvants and their immunological mechanisms of action
TL;DR: It is emphasised that aluminium adjuvants used in clinically approved vaccines are chemically and biologically dissimilar with concomitantly potentially distinct roles in vaccine-related adverse events.
Journal ArticleDOI
Neutrophil swarming and extracellular trap formation play a significant role in Alum adjuvant activity.
TL;DR: It is shown that alum artificially stimulates this pathway to boost the adaptive immune response to vaccine antigens, increasing their immunogenicity and the authors suggest further study into neutrophil components as potential therapeutic agents.
Journal ArticleDOI
TANK-Binding Kinase 1-Dependent Responses in Health and Autoimmunity.
TL;DR: The role of TBK1 in immunological pathways involved in the development and maintenance of antibody responses, with particular emphasis on its potential relevance in the pathogenesis of humoral autoimmunity, is discussed.
Journal ArticleDOI
Neutrophil Extracellular Traps Downregulate Lipopolysaccharide-Induced Activation of Monocyte-Derived Dendritic Cells
Lorena Barrientos,Alexandre Bignon,Claire Gueguen,Luc de Chaisemartin,Roseline Gorges,Catherine Sandré,Laurent Mascarell,Karl Balabanian,Saadia Kerdine-Römer,Marc Pallardy,Viviana Marin-Esteban,Sylvie Chollet-Martin +11 more
TL;DR: A new role for NETs in adaptive immune responses is revealed, modulating some moDC functions and thereby participating in the control of inflammation.
References
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Osamu Takeuchi,Shizuo Akira +1 more
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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
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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.