DNA released from dying host cells mediates aluminum adjuvant activity
DNA released from dying host cells mediates aluminum adjuvant activity
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DOI：
10.1038/nm.2403
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发表时间：
2011-08-01
期刊：
影响因子：
82.9
通讯作者：
Desmet, Christophe J.
中科院分区：
文献类型：
--
作者：
Marichal, Thomas;Ohata, Keiichi;Desmet, Christophe J.
铝基佐剂（铝盐或明矾）广泛用于人类疫苗接种，但其作用机制知之甚少。在这里，我们报告说，在小鼠中，明矾引起细胞死亡和随后释放宿主细胞DNA，这作为一个强大的内源性免疫刺激信号介导明矾佐剂活性。此外，我们建议，宿主DNA信号差异调节IgE和IgG1生产明矾佐剂免疫后。我们认为，一方面，宿主DNA诱导主要B细胞的反应，包括IgG 1的生产，通过干扰素反应因子3（Irf 3）的独立机制。另一方面，我们认为，宿主DNA也刺激“典型的”T辅助细胞2型（T（H）2）的反应，与IgE同种型转换和外周效应反应，通过Irf3依赖的机制。从垂死细胞释放的宿主DNA作为介导明矾佐剂活性的损伤相关分子模式的发现可能增加我们对当前疫苗作用机制的理解，并有助于设计新的佐剂。
Aluminum-based adjuvants (aluminum salts or alum) are widely used in human vaccination, although their mechanisms of action are poorly understood. Here we report that, in mice, alum causes cell death and the subsequent release of host cell DNA, which acts as a potent endogenous immunostimulatory signal mediating alum adjuvant activity. Furthermore, we propose that host DNA signaling differentially regulates IgE and IgG1 production after alum-adjuvanted immunization. We suggest that, on the one hand, host DNA induces primary B cell responses, including IgG1 production, through interferon response factor 3 (Irf3)-independent mechanisms. On the other hand, we suggest that host DNA also stimulates 'canonical' T helper type 2 (T(H)2) responses, associated with IgE isotype switching and peripheral effector responses, through Irf3-dependent mechanisms. The finding that host DNA released from dying cells acts as a damage-associated molecular pattern that mediates alum adjuvant activity may increase our understanding of the mechanisms of action of current vaccines and help in the design of new adjuvants.