The Vaccine Adjuvant Chitosan Promotes Cellular Immunity via DNA Sensor cGAS-STING-Dependent Induction of Type I Interferons.
The Vaccine Adjuvant Chitosan Promotes Cellular Immunity via DNA Sensor cGAS-STING-Dependent Induction of Type I Interferons.
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DOI：
10.1016/j.immuni.2016.02.004
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发表时间：
2016-03-15
期刊：
影响因子：
32.4
通讯作者：
Lavelle EC
中科院分区：
文献类型：
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作者：
Carroll EC;Jin L;Mori A;Muñoz-Wolf N;Oleszycka E;Moran HBT;Mansouri S;McEntee CP;Lambe E;Agger EM;Andersen P;Cunningham C;Hertzog P;Fitzgerald KA;Bowie AG;Lavelle EC
阳离子多糖壳聚糖是一种有吸引力的候选佐剂，能够驱动有效的细胞介导免疫，但其作用机制尚不清楚。我们发现壳聚糖通过诱导I型干扰素（IFN）促进树突状细胞成熟，并以I型IFN受体依赖的方式增强抗原特异性T辅助1 （Th1）反应。壳聚糖诱导I型ifn、ifn刺激基因和树突状细胞成熟需要细胞质DNA传感器cGAS和STING，暗示这一途径参与了树突状细胞的激活。此外，这一过程依赖于线粒体活性氧和细胞质DNA的存在。接种后壳聚糖介导的抗原特异性Th1和免疫球蛋白G2c反应的增强依赖于cGAS和STING。这些发现表明，阳离子聚合物可以参与STING-cGAS通路，触发先天和适应性免疫反应。
The cationic polysaccharide chitosan is an attractive candidate adjuvant capable of driving potent cell-mediated immunity, but the mechanism by which it acts is not clear. We show that chitosan promotes dendritic cell maturation by inducing type I interferons (IFNs) and enhances antigen-specific T helper 1 (Th1) responses in a type I IFN receptor-dependent manner. The induction of type I IFNs, IFN-stimulated genes and dendritic cell maturation by chitosan required the cytoplasmic DNA sensor cGAS and STING, implicating this pathway in dendritic cell activation. Additionally, this process was dependent on mitochondrial reactive oxygen species and the presence of cytoplasmic DNA. Chitosan-mediated enhancement of antigen specific Th1 and immunoglobulin G2c responses following vaccination was dependent on both cGAS and STING. These findings demonstrate that a cationic polymer can engage the STING-cGAS pathway to trigger innate and adaptive immune responses.