Cutting edge: inflammasome activation by alum and alum's adjuvant effect are mediated by NLRP3.
Cutting edge: inflammasome activation by alum and alum's adjuvant effect are mediated by NLRP3.
复制标题
DOI：
10.4049/jimmunol.181.1.17
复制
发表时间：
2008-07-01
影响因子：
4.4
通讯作者：
Re, Fabio
中科院分区：
文献类型：
--
作者：
Li, Hanfen;Willingham, Stephen B.;Ting, Jenny P. -Y.;Re, Fabio
明矾是唯一被批准用于人类常规使用的佐剂，尽管其佐剂的基础仍然知之甚少。我们最近发现明矾激活caspase-1并诱导成熟IL-1β和IL-18的分泌。本研究表明，在人和小鼠巨噬细胞中，铝诱导的IL-1β、IL-18和IL-33分泌是由NLR蛋白NLRP3及其接头ASC介导的，而不是NLRC4。其他颗粒佐剂，如QuilA和壳聚糖，以nlrp3依赖的方式诱导炎症小体激活，这表明nlrp3炎症小体的激活可能是颗粒佐剂的共同作用机制。重要的是，我们证明了含有明矾的疫苗在nlrp3缺陷小鼠中引起的抗原特异性抗体产生明显受损。我们的研究结果首次证明了nlrp3炎性体在铝增强疫苗引起的免疫反应发展过程中的作用。并提示针对NLRP3的治疗性干预可提高辅助疗效。
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-1β and IL-18. Here we show that in human and mice macrophages, alum-induced IL-1β, IL-18, and IL-33 secretion is mediated by the NLR 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 antigen-specific antibody 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.
登录
查看更多内容
影响因子：
6.4
作者：
Pollock, KGJ;Conacher, M;Brewer, JM
通讯作者：
Brewer, JM
影响因子：
5.5
作者：
Sun, HF;Pollock, KGJ;Brewer, JM
通讯作者：
Brewer, JM
影响因子：
56.9
作者：
Jordan, MB;Mills, DM;Cambier, JC
通讯作者：
Cambier, JC
影响因子：
30.5
作者：
Franchi, Luigi;Amer, Amal;Nunez, Gabriel
通讯作者：
Nunez, Gabriel
影响因子：
32.4
作者：
Agostini, L;Martinon, F;Tschopp, J
通讯作者：
Tschopp, J