Laboratory of Cellular and Molecular Physiology, Groupe Interdisciplinaire de Génoprotéomique Appliquée, University of Liège, Liège, Belgium.
Nat Med. 2011 Jul 17;17(8):996-1002. doi: 10.1038/nm.2403.
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.
铝佐剂（铝盐或明矾）广泛用于人类疫苗接种，尽管其作用机制尚不清楚。在这里，我们报告称，在小鼠中，明矾会导致细胞死亡，随后释放宿主细胞 DNA，后者作为一种有效的内源性免疫刺激信号，介导明矾佐剂活性。此外，我们提出宿主 DNA 信号对明矾佐剂免疫接种后 IgE 和 IgG1 产生的调节存在差异。我们认为，一方面，宿主 DNA 通过干扰素反应因子 3（Irf3）非依赖性机制诱导初级 B 细胞反应，包括 IgG1 的产生。另一方面，我们认为宿主 DNA 还通过 Irf3 依赖性机制刺激“经典”辅助性 T 细胞 2（T(H)2）反应，与 IgE 同种型转换和外周效应器反应相关。从死亡细胞中释放的宿主 DNA 作为一种损伤相关分子模式发挥作用，介导明矾佐剂活性，这一发现可能有助于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。
