Alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome
Alum adjuvant stimulates inflammatory dendritic cells through activation of the NALP3 inflammasome
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DOI：
10.4049/jimmunol.181.6.3755
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发表时间：
2008-09-15
影响因子：
4.4
通讯作者：
Tschopp, Juerg
中科院分区：
文献类型：
--
作者：
Kool, Mirjam;Petrilli, Virginie;Tschopp, Juerg
佐剂是疫苗添加剂，其刺激免疫系统而本身没有任何特异性抗原作用。在这项研究中，我们表明明矾佐剂诱导巨噬细胞和树突状细胞释放IL-1 β，并且在缺乏各种NALP 3炎性体组分的细胞中这被废除。NALP 3炎性体也是体内对明矾中的OVA的先天免疫应答所需的。在NALP 3缺陷小鼠中，IL-1 β的早期产生和炎症细胞流入腹膜腔的数量大大减少。对OVA-明矾的适应性细胞免疫的激活由单核细胞树突状细胞前体启动，其以NALP 3依赖性方式诱导Ag特异性T细胞的扩增。我们建议，除了TLR刺激剂之外，NALP 3炎性体的激动剂也应该被认为是疫苗佐剂。
Adjuvants are vaccine additives that stimulate the immune system without having any specific antigenic effect of itself. In this study we show that alum adjuvant induces the release of IL-1 beta from macrophages and dendritic cells and that this is abrogated in cells lacking various NALP3 inflammasome components. The NALP3 inflammasome is also required in vivo for the innate immune response to OVA in alum. The early production of IL-1 beta and the influx of inflammatory cells into the peritoneal cavity is strongly reduced in NALP3-deficient mice. The activation of adaptive cellular immunity to OVA-alum is initiated by monocytic dendritic cell precursors that induce the expansion of Ag-specific T cells in a NALP3-dependent way. We propose that, in addition to TLR stimulators, agonists of the NALP3 inflammasome should also be considered as vaccine adjuvants.