Synthetic mast-cell granules as adjuvants to promote and polarize immunity in lymph nodes.

Synthetic mast-cell granules as adjuvants to promote and polarize immunity in lymph nodes.
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DOI:
10.1038/nmat3222
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发表时间:
2012-01-22
期刊:
影响因子:
41.2
通讯作者:
--
中科院分区:
材料科学1区
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--
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肥大细胞(MC)的颗粒在激活时作为稳定颗粒释放,从而增强适应性免疫。在这里,我们表明,亚微米粒子模仿MC颗粒增强免疫力时,用作疫苗中的佐剂。合成颗粒由碳水化合物骨架和包封的炎症介质如肿瘤坏死因子组成,在体内复制MC的属性,包括靶向引流淋巴结和包封介质的定时释放。当在用流感病毒的血凝素给小鼠接种疫苗期间用作佐剂时,颗粒增强了适应性免疫应答,并增加了小鼠在致命攻击中的存活率。此外,细胞因子IL-12的颗粒的差异负载指导了对Th 1淋巴细胞的响应的特征。合成的MC佐剂在疫苗接种期间复制并增强MC的功能,并且可以扩展以增强所产生的免疫。
Granules of mast cells (MCs) enhance adaptive immunity when, on activation, they are released as stable particles. Here we show that submicrometre particles modelled after MC granules augment immunity when used as adjuvants in vaccines. The synthetic particles, which consist of a carbohydrate backbone with encapsulated inflammatory mediators such as tumour necrosis factor, replicate attributes of MCs in vivo including the targeting of draining lymph nodes and the timed release of the encapsulated mediators. When used as an adjuvant during vaccination of mice with haemagglutinin from the influenza virus, the particles enhanced adaptive immune responses and increased survival of mice on lethal challenge. Furthermore, differential loading of the particles with the cytokine IL-12 directed the character of the response towards Th1 lymphocytes. The synthetic MC adjuvants replicate and enhance the functions of MCs during vaccination, and can be extended to polarize the resulting immunity.
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