Aluminum Hydroxide Adjuvants Activate Caspase-1 and Induce IL-1β and IL-18 Release
Hanfen Li,Suba Nookala,Fabio Re +2 more
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TLDR
It is shown that Alum activates caspase-1 and induce secretion of mature IL-1β and IL-18, and a mechanism for the adjuvanticity of Alum is suggested.Abstract:
Aluminum hydroxide (Alum) is the only adjuvant approved for routine use in humans, although the basis for its adjuvanticity remains poorly understood. In this study, we show that Alum activates caspase-1 and induce secretion of mature IL-1beta and IL-18. Human PBMC or dendritic cells stimulated with pure TLR4 and TLR2 agonists released only traces of IL-1beta or IL-18, despite the fact that the IL-1beta mRNA was readily induced by both TLR agonists. In contrast, cells costimulated with TLR agonists plus Alum released large amount of IL-1beta and IL-18. Alum-induced IL-1beta and IL-18 production was not due to enhancement of TLR signaling but rather reflected caspase-1 activation and in mouse dendritic cells occurred in a MyD88-independent fashion. Secretion of other proinflammatory cytokines such as IL-8 was not affected by Alum treatments. However, TLR-induced production of IL-10 was increased and that of IFN-gamma-inducible protein decreased by Alum cotreatment. Considering the immunostimulatory activities of these cytokines and the ability of IL-1beta to act as adjuvant, our results suggest a mechanism for the adjuvanticity of Alum.read more
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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.
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The Inflammasomes: Guardians of the Body
TL;DR: The role of NLRs, and in particular the inflammasomes, in the recognition of microbial and danger components and the role they play in health and disease are discussed.
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Vaccine Adjuvants: Putting Innate Immunity to Work
TL;DR: There remains a need for improved adjuvants that enhance protective antibody responses, especially in populations that respond poorly to current vaccines, and the larger challenge is to develop vaccines that generate strong T cell immunity with purified or recombinant vaccine antigens.
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Crucial role for the Nalp3 inflammasome in the immunostimulatory properties of aluminium adjuvants.
Stephanie C. Eisenbarth,Oscar R. Colegio,William T. O'Connor,Fayyaz S. Sutterwala,Richard A. Flavell +4 more
TL;DR: It is shown that aluminium adjuvants activate an intracellular innate immune response system called the Nalp3 (also known as cryopyrin, CIAS1 or NLRP3) inflammasome, which is a crucial element in the adjuvant effect of aluminium adjvants.
Journal ArticleDOI
Alum adjuvant boosts adaptive immunity by inducing uric acid and activating inflammatory dendritic cells
Mirjam Kool,Thomas Soullié,Menno van Nimwegen,Monique Willart,Femke Muskens,Steffen Jung,Henk C. Hoogsteden,Hamida Hammad,Bart N. Lambrecht +8 more
TL;DR: Mechanistically, DC-driven responses were abolished in MyD88-deficient mice and after uricase treatment, implying the induction of uric acid, and suggest that alum adjuvant is immunogenic by exploiting “nature's adjUvant,” the inflammatory DC through induction of the endogenous danger signal uric acids.
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