Journal
JOURNAL OF IMMUNOLOGY
Volume 181, Issue 1, Pages 17-21Publisher
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.181.1.17
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Funding
- NIAID NIH HHS [R21 AI076835-01, R21 AI076835, U54 AI057157, R01 AI063031, R01AI063031, R01AI057157, U54 AI057157-010006, R21AI076835-01, R01 AI063031-04] Funding Source: Medline
- NIDCR NIH HHS [R01DE16326, R01 DE016326, R01 DE016326-04] Funding Source: Medline
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Alum is the only adjuvant approved for routine use in humans, although the basis for its adjuvanticity remains poorly understood. We have recently shown that alum activates caspase-1 and induces secretion of mature IL-1 beta and IL-18. In this study we show that, in human and mouse macrophages, alum-induced secretion of IL-1 beta, IL-18, and IL-33 is mediated by the NLR (nucleotide-binding domain leucine-rich repeat-containing) protein NLRP3 and its adaptor ASC, but not by NLRC4. Other particulate adjuvants, such as QuilA and chitosan, induce inflammasome activation in a NLRP3-dependent fashion, suggesting that activation of the NLRP3-inflammasome may be a common mechanism of action of particulate adjuvants. Importantly, we demonstrate that Ag-specific Ab production elicited by vaccines that contain alum is significantly impaired in NLRP3-deficient mice. Our results demonstrate for the first time a role for the NLRP3-inflammasome during development of the immune response elicited by alum-enhanced vaccination and suggest that therapeutic intervention aimed at NLRP3 may improve adjuvant efficacy.
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