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细菌机械裂解物的混合物比单一菌株裂解物和细菌来源的可溶性产物更有效地诱导人树突状细胞的激活表型。

A mixture of bacterial mechanical lysates is more efficient than single strain lysate and of bacterial-derived soluble products for the induction of an activating phenotype in human dendritic cells.

机构信息

Laboratorio di Immunologia, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.

出版信息

Immunol Lett. 2011 Jul;138(1):86-91. doi: 10.1016/j.imlet.2011.03.006. Epub 2011 Mar 29.

DOI:10.1016/j.imlet.2011.03.006
PMID:21453728
Abstract

Dendritic cells (DCs), following an optimal maturation, are able to drive an efficient immune-response. For this, both co-stimulatory molecules (CD80 and CD86), activation molecules (CD83) and peptide presenting molecules (HLA) are over-expressed. The in vitro treatment of immature DC with fragments of bacterial strains, obtained by using a mechanical lysis as well as with bacterial-derived molecules (such as lipopolysaccharide and protido-glycan), induced the maturation of DCs and the secretion of a panel of cytokines and chemokines. Of note, ex vivo treated circulating DCs and plasmacytoid DCs were also activated by these bacterial bodies. However, while the particulate fraction of single bacterial strains or soluble bacterial-derived molecules induced a sub-optimal maturation (as evaluated by the expression of an activating phenotype on DCs and the amount of cytokine secretion), the addition of the mixture of the particulate fractions of the different bacterial strains was able to mediate an optimal maturation. These results were also confirmed by using the secretion of both cytokines and chemokines as markers of DC activation. All these findings suggest that the particulate fraction of bacterial lysate mixtures, because of their ability to interact with different surface structures, might be exploited not only as an immunogen, but also as an adjuvant treatment to boost an immune-response to poorly "antigenic" proteins, such as cancer antigens or allergens.

摘要

树突状细胞 (DCs) 在经过最佳成熟后,能够驱动有效的免疫反应。为此,共刺激分子 (CD80 和 CD86)、激活分子 (CD83) 和肽呈递分子 (HLA) 均过度表达。通过机械裂解获得的细菌片段以及细菌衍生分子(如脂多糖和糖蛋白)对未成熟 DC 的体外处理,诱导了 DC 的成熟和一系列细胞因子和趋化因子的分泌。值得注意的是,这些细菌体还激活了体外处理的循环 DC 和浆细胞样 DC。然而,虽然单一细菌株的颗粒部分或可溶性细菌衍生分子诱导了亚最佳成熟(如通过 DC 上激活表型的表达和细胞因子分泌的量来评估),但不同细菌株的颗粒部分混合物的添加能够介导最佳成熟。这些结果也通过使用细胞因子和趋化因子的分泌作为 DC 激活的标志物来证实。所有这些发现表明,细菌裂解物混合物的颗粒部分由于其与不同表面结构相互作用的能力,不仅可以用作免疫原,还可以用作佐剂治疗,以增强对“抗原性”差的蛋白质(如癌症抗原或过敏原)的免疫反应。

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