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