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转染携带衣原体外膜主要蛋白抗原的重组腺病毒的树突状细胞可引发针对生殖道挑战感染的保护性免疫应答。

Dendritic cells (DCs) transfected with a recombinant adenovirus carrying chlamydial major outer membrane protein antigen elicit protective immune responses against genital tract challenge infection.

机构信息

Department of Medical Microbiology, Shandong Univeristy School of Medicine, Jinan, Shandong, P.R. China.

出版信息

Biochem Cell Biol. 2010 Aug;88(4):757-65. doi: 10.1139/O10-011.

Abstract

Chlamydia trachomatis, an obligate intracellular bacterial pathogen, is the major cause of sexually transmitted diseases worldwide. Although a variety of strategies have been taken to promote the development of a protective vaccine, no ideal vaccine has been generated so far. In this study, we transfected dendritic cells (DCs) with recombinant adenovirus carrying C. trachomatis serovar E major outer membrane protein gene (Ad-MOMP), and investigated their ability to induce specific protection against genital tract chlamydial challenge infection. The results showed that when DCs were transfected with Ad-MOMP in vitro, the DCs exhibited increased expression of CD80 and MHC-II molecules as well as enhanced IL-12 secretion and were able to stimulate T-cell proliferation. The level of IFN-gamma secreted by stimulated T cells was also up-regulated significantly. When the Ad-MOMP transfected DCs were adoptively transferred intravenously to naive mice, they generated Th1-biased cytokine production and mucosal IgA responses specific for C. trachomatis. More importantly, the mice immunized with Ad-MOMP-DC mounted protection against genital tract challenge infection, shown by lower body mass loss, lower chlamydial loads, and less severe pathological changes. In conclusion, Ad-MOMP transfected DCs are capable of inducing effective protective immune responses against C. trachomatis genital infection.

摘要

沙眼衣原体是一种专性细胞内细菌病原体,是全球性传播疾病的主要原因。尽管已经采取了多种策略来促进保护性疫苗的开发,但迄今为止还没有产生理想的疫苗。在本研究中,我们用携带沙眼衣原体血清型 E 主要外膜蛋白基因的重组腺病毒(Ad-MOMP)转染树突状细胞(DCs),并研究了它们诱导针对生殖道沙眼衣原体挑战感染的特异性保护的能力。结果表明,当 DCs 在体外转染 Ad-MOMP 时,DCs 表达 CD80 和 MHC-II 分子的水平增加,IL-12 的分泌增强,并能刺激 T 细胞增殖。刺激 T 细胞分泌的 IFN-γ水平也显著上调。当转染 Ad-MOMP 的 DCs 被静脉内过继转移到未致敏小鼠中时,它们产生针对沙眼衣原体的 Th1 偏向细胞因子产生和黏膜 IgA 反应。更重要的是,用 Ad-MOMP-DC 免疫的小鼠对生殖道挑战感染产生了保护作用,表现为体重减轻减少、衣原体负荷降低和病变程度减轻。总之,转染 Ad-MOMP 的 DCs 能够诱导针对沙眼衣原体生殖道感染的有效保护性免疫应答。

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