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婴儿利什曼原虫 LeIF 及其重组多肽在体外诱导树突状细胞的成熟:基于树突状细胞的疫苗的新见解。

Leishmania infantum LeIF and its recombinant polypeptides induce the maturation of dendritic cells in vitro: An insight for dendritic cells based vaccine.

机构信息

Laboratory of Molecular Epidemiology and Experimental Pathology, Institut Pasteur de Tunis, Université Tunis El Manar, 13 Place Pasteur, BP 74, 1002 Tunis-Belvedère, Tunisia.

Laboratory of Cellular Immunology, Department of Microbiology, Hellenic Pasteur Institute, 127 Vass Sofias Av, Athens 11521, Greece.

出版信息

Immunol Lett. 2019 Jun;210:20-28. doi: 10.1016/j.imlet.2019.04.001. Epub 2019 Apr 15.

DOI:10.1016/j.imlet.2019.04.001
PMID:30998957
Abstract

We previously showed that recombinant Leishmania infantum eukaryotic initiation factor (LieIF) was able to induce the secretion of cytokines IL-12, IL-10 and TNF-α by human monocytes. In this study, we explored in vitro the potential of LieIF to induce phenotypic maturation and functional differentiation of murine bone-marrow derived dendritic cells (BM-DCs). Moreover, in order to identify potential immunnomodulatory regions of LieIF, eight recombinant overlapping protein fragments covering the whole amino acid sequence of protein, were constructed and assessed in vitro for their ability to induce maturation of BM-DCs. Our data showed that LieIF and some of its recombinant polypeptides were able to induce elevated expression of CD40, CD80 and CD86 co-stimulatory molecules with concurrent IL-12 production. Moreover, we used an in vivo experimental model of cutaneous leishmaniasis consisted of susceptible Leishmania major-infected BALB/c mice and we demonstrated that LieIF-pulsed-BM-DCs adoptively transferred in mice were capable to confer protection against a high dose parasite challenge. This study further describes the immunomodulatory properties of LieIF and its polypeptides bringing relevant information for their exploitation as candidate molecules for vaccine development against leishmaniasis.

摘要

我们之前曾表明,重组利什曼原虫真核起始因子(LieIF)能够诱导人单核细胞分泌细胞因子 IL-12、IL-10 和 TNF-α。在这项研究中,我们探讨了 LieIF 在体外诱导鼠骨髓来源树突状细胞(BM-DC)表型成熟和功能分化的潜力。此外,为了鉴定 LieIF 的潜在免疫调节区域,构建了 8 个覆盖该蛋白全长氨基酸序列的重组重叠蛋白片段,并评估了它们诱导 BM-DC 成熟的能力。我们的数据表明,LieIF 和其一些重组多肽能够诱导共刺激分子 CD40、CD80 和 CD86 的高表达,并伴有 IL-12 的产生。此外,我们使用了皮肤利什曼病的体内实验模型,即易感的感染利什曼原虫的 BALB/c 小鼠,并证明了在小鼠中过继转移的经 LieIF 脉冲的 BM-DC 能够抵御高剂量寄生虫的攻击。这项研究进一步描述了 LieIF 及其多肽的免疫调节特性,为它们作为利什曼病疫苗开发的候选分子提供了相关信息。

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Leishmania infantum LeIF and its recombinant polypeptides induce the maturation of dendritic cells in vitro: An insight for dendritic cells based vaccine.婴儿利什曼原虫 LeIF 及其重组多肽在体外诱导树突状细胞的成熟:基于树突状细胞的疫苗的新见解。
Immunol Lett. 2019 Jun;210:20-28. doi: 10.1016/j.imlet.2019.04.001. Epub 2019 Apr 15.
2
Leishmania infantum LeIF and its recombinant polypeptides modulate interleukin IL-12p70, IL-10 and tumour necrosis factor-α production by human monocytes.婴儿利什曼原虫 LeIF 及其重组多肽调节人单核细胞产生白细胞介素 IL-12p70、IL-10 和肿瘤坏死因子-α。
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In silico analysis and in vitro evaluation of immunogenic and immunomodulatory properties of promiscuous peptides derived from Leishmania infantum eukaryotic initiation factor.婴儿利什曼原虫真核起始因子衍生的混杂肽免疫原性和免疫调节特性的计算机模拟分析及体外评估
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New Insights on the Adjuvant Properties of the Eukaryotic Initiation Factor.真核起始因子的佐剂特性的新见解
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Cellular vaccination with bone marrow-derived dendritic cells pulsed with a peptide of Leishmania infantum KMP-11 and CpG oligonucleotides induces protection in a murine model of visceral leishmaniasis.用骨髓来源的树突状细胞接种细胞,用利什曼原虫婴儿 KMP-11 肽和 CpG 寡核苷酸冲击,可在内脏利什曼病的小鼠模型中诱导保护作用。
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Dendritic cell (DC)-based protection against an intracellular pathogen is dependent upon DC-derived IL-12 and can be induced by molecularly defined antigens.基于树突状细胞(DC)对细胞内病原体的保护作用依赖于DC衍生的白细胞介素-12,并且可以由分子定义的抗原诱导产生。
J Immunol. 2003 Mar 15;170(6):3171-9. doi: 10.4049/jimmunol.170.6.3171.
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Leishmania eukaryotic initiation factor (LeIF) inhibits parasite growth in murine macrophages.利什曼原虫真核起始因子(LeIF)抑制寄生虫在小鼠巨噬细胞中的生长。
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Immunization with a recombinant stage-regulated surface protein from Leishmania donovani induces protection against visceral leishmaniasis.用来自杜氏利什曼原虫的重组阶段调节表面蛋白进行免疫接种可诱导对内脏利什曼病的保护作用。
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LeIF: a recombinant Leishmania protein that induces an IL-12-mediated Th1 cytokine profile.LeIF:一种可诱导白细胞介素-12介导的辅助性T细胞1型细胞因子谱的重组利什曼原虫蛋白。
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Induction of protective cellular immune responses against experimental visceral leishmaniasis mediated by dendritic cells pulsed with the N-terminal domain of Leishmania infantum elongation factor-2 and CpG oligodeoxynucleotides.用利什曼原虫延伸因子-2 的 N 端结构域和 CpG 寡脱氧核苷酸脉冲处理树突状细胞,诱导针对实验内脏利什曼病的保护性细胞免疫应答。
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