The Nlrp3 inflammasome is critical for aluminium hydroxide-mediated IL-1beta secretion but dispensable for adjuvant activity.
The Nlrp3 inflammasome is critical for aluminium hydroxide-mediated IL-1beta secretion but dispensable for adjuvant activity.
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DOI：
10.1002/eji.200838549
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发表时间：
2008-08
影响因子：
5.4
通讯作者：
Nunez, Gabriel
中科院分区：
文献类型：
--
作者：
Franchi, Luigi;Nunez, Gabriel
明矾（氢氧化铝）是人类疫苗中最广泛使用的佐剂，但对明矾激活的免疫机制仍知之甚少。明矾最近已被证明可促进半胱天冬酶-1活化和IL-1β分泌，但所涉及的细胞途径仍然难以捉摸。在这里，我们报告了由明矾触发的IL-1β的释放在Nlrp 3和Asc缺陷的巨噬细胞中被废除，但Nlrc 4没有。Nlrp 3炎性小体对IL-1β的需求是特异性的，因为TNF-α的分泌不依赖于Nlrp 3或Asc。因此，在缺乏Nlrp 3或Asc的巨噬细胞中，明矾诱导的caspase-1前体加工被取消。与LPS触发的caspase-1加工和IL-1β分泌不同，明矾介导的炎性体激活不需要外源性ATP。重要的是，在Nlrp 3缺陷的小鼠中，明矾诱导产生抗人血清白蛋白的IgG未受损。这些结果表明明矾通过Nlrp 3炎性体诱导IL-1β，但该活性与明矾介导的佐剂活性无关。
Alum (aluminiun hydroxide) is the most widely used adjuvant in human vaccines, but the immune mechanisms that are activated by alum remain poorly understood. Alum has been recently shown to promote caspase-1 activation and IL-1β secretion but the cellular pathways involved remain elusive. Here we report that the release of IL-1β triggered by alum is abrogated in macrophages deficient in Nlrp3 and Asc but not Nlrc4. The requirement of the Nlrp3 inflammasome was specific for IL-1β in that secretion of TNF-α was independent of Nlrp3 or Asc. Consistently, processing of pro-caspase-1 induced by alum was abolished in macrophages lacking Nlrp3 or Asc. Unlike caspase-1 processing and IL-1β secretion triggered by LPS, alum-mediated activation of the inflammasome did not require exogenous ATP. Importantly, induction of IgG production against human serum albumin by alum was unimpaired in mice deficient in Nlrp3. These results indicate that alum induces IL-1β via the Nlrp3 inflammasome but this activity is dispensable for alum-mediated adjuvant activity.
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影响因子：
30.5
作者：
Franchi, Luigi;Amer, Amal;Nunez, Gabriel
通讯作者：
Nunez, Gabriel
影响因子：
5.5
作者：
Sokolovska, Anna;Hem, Stanley L.;HogenEsch, Harm
通讯作者：
HogenEsch, Harm
影响因子：
32.4
作者：
Sutterwala, FS;Ogura, Y;Flavell, RA
通讯作者：
Flavell, RA
影响因子：
56.9
作者：
Dostert, Catherine;Petrilli, Virginie;Tschopp, Jurg
通讯作者：
Tschopp, Jurg
影响因子：
64.8
作者：
Kanneganti, TD;Özören, N;Núñez, G
通讯作者：
Núñez, G