Suschak John J, Wang Shixia, Fitzgerald Katherine A, Lu Shan
Laboratory of Nucleic Acid Vaccines, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655; and.
Program in Innate Immunity, Division of Infectious Diseases, Department of Medicine, University of Massachusetts Medical School, Worcester, MA 01655.
J Immunol. 2015 Jan 15;194(2):630-6. doi: 10.4049/jimmunol.1402530. Epub 2014 Dec 8.
Recent human study data have re-established the value of DNA vaccines, especially in priming high-level Ag-specific Ab responses, but also raised questions about the mechanisms responsible for such effects. Whereas previous reports have shown involvement of downstream signaling molecules in the innate immune system, the current study investigated the role of absent in melanoma 2 (Aim2) as a sensor for DNA vaccines. The Aim2 inflammasome directs maturation of the proinflammatory cytokines IL-1β and IL-18 and an inflammatory form of cell death called pyroptosis. Both the humoral and cellular Ag-specific adaptive responses were significantly reduced in Aim2-deficient mice in an IL-1β/IL-18-independent manner after DNA vaccination. Surprisingly, Aim2-deficient mice also exhibited significantly lower levels of IFN-α/β at the site of injection. These results indicate a previously unreported link between DNA vaccine-induced pyroptotic cell death and vaccine immunogenicity that is instrumental in shaping the Ag-specific immune response to DNA vaccines.
最近的人体研究数据重新确立了DNA疫苗的价值，尤其是在引发高水平的抗原特异性抗体反应方面，但也引发了关于造成此类效应的机制的问题。尽管之前的报告显示下游信号分子参与了先天免疫系统，但当前的研究调查了黑色素瘤缺失2（Aim2）作为DNA疫苗传感器的作用。Aim2炎性小体指导促炎细胞因子IL-1β和IL-18的成熟以及一种称为细胞焦亡的炎性细胞死亡形式。DNA疫苗接种后，Aim2缺陷小鼠的体液和细胞抗原特异性适应性反应均以不依赖IL-1β/IL-18的方式显著降低。令人惊讶的是，Aim2缺陷小鼠在注射部位的IFN-α/β水平也显著降低。这些结果表明DNA疫苗诱导的细胞焦亡与疫苗免疫原性之间存在以前未报道的联系，这有助于塑造针对DNA疫苗的抗原特异性免疫反应。
