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由噬菌体φX174基因诱导产生的伤寒杆菌幽灵刺激树突状细胞并有效激活适应性免疫反应。

A Typhi ghost induced by the gene of phage φX174 stimulates dendritic cells and efficiently activates the adaptive immune response.

作者信息

Won Gayeon, Eo Seong Kug, Park Sang-Youel, Hur Jin, Lee John Hwa

机构信息

College of Veterinary Medicine, Chonbuk National University, Iksan Campus, Iksan 54596, Korea.

出版信息

J Vet Sci. 2018 Jul 31;19(4):536-542. doi: 10.4142/jvs.2018.19.4.536.

Abstract

Previously, we genetically engineered a Typhi bacterial ghost (STG) as a novel inactivated vaccine candidate against typhoid fever. The underlying mechanism employed by the ghost in stimulating the adaptive immune response remains to be investigated. In this study, we aimed to evaluate the immunostimulatory effect of STG on mouse bone marrow-derived dendritic cells (BMDCs) and its activation of the adaptive immune response . Immature BMDCs were stimulated with STG, which efficiently stimulated maturation events in BMDCs, as indicated by upregulated expressions of CD40, CD80, and major histocompatibility complex class II molecules on CD11 BMDCs. Immature BMDCs responded to STG stimulation by significantly increasing the expression of interleukin (IL)-6, which might indicate the induction of dendritic cell maturation ( < 0.05). In addition, ghost-stimulated murine BMDCs showed significant expressions of interferon gamma and IL-4, which can drive the development of Th1 and Th2 cells, respectively, in co-cultured CD4 T cells . These results suggest that STG can effectively stimulate maturation of BMDCs and facilitate subsequent immune responses via potent immunomodulatory cytokine responses.

摘要

此前,我们通过基因工程构建了一种伤寒杆菌菌影(STG),作为一种新型的伤寒热灭活疫苗候选物。菌影刺激适应性免疫反应的潜在机制仍有待研究。在本研究中,我们旨在评估STG对小鼠骨髓来源的树突状细胞(BMDC)的免疫刺激作用及其对适应性免疫反应的激活作用。用STG刺激未成熟的BMDC,STG能有效刺激BMDC的成熟过程,这表现为CD11 BMDC上CD40、CD80和主要组织相容性复合体II类分子的表达上调。未成熟的BMDC对STG刺激的反应是白细胞介素(IL)-6的表达显著增加,这可能表明树突状细胞成熟的诱导(P<0.05)。此外,菌影刺激的小鼠BMDC显示出干扰素γ和IL-4的显著表达,它们分别可以在共培养的CD4 T细胞中驱动Th1和Th2细胞的发育。这些结果表明,STG可以通过强大的免疫调节细胞因子反应有效刺激BMDC的成熟并促进随后的免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/75b8/6070585/4acd50d2190c/jvs-19-536-g001.jpg

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