| First Author | Li H | Year | 2008 |
| Journal | J Immunol | Volume | 181 |
| Issue | 1 | Pages | 17-21 |
| PubMed ID | 18566365 | Mgi Jnum | J:137363 |
| Mgi Id | MGI:3799393 | Doi | 10.4049/jimmunol.181.1.17 |
| Citation | Li H, et al. (2008) Cutting edge: inflammasome activation by alum and alum's adjuvant effect are mediated by NLRP3. J Immunol 181(1):17-21 |
| abstractText | 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-1beta and IL-18. In this study we show that, in human and mouse macrophages, alum-induced secretion of IL-1beta, 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. |
