Devender Moodu, Sebastian Prince, Maurya Vijay Kumar, Kumar Krishan, Anand Anjali, Namdeo Madhulika, Maurya Radheshyam
Department of Animal Biology, School of Life Sciences, University of Hyderabad, Hyderabad, India.
Front Immunol. 2024 Jan 11;14:1294397. doi: 10.3389/fimmu.2023.1294397. eCollection 2023.
Visceral leishmaniasis (VL) is referred to as the most severe and fatal type of leishmaniasis basically caused by and . The most effective method for preventing the spread of the disease is vaccination. Till today, there is no promising licensed vaccination for human VL. Hence, investigation for vaccines is necessary to enrich the therapeutic repertoire against leishmaniasis. Tuzin is a rare trans-membrane protein that has been reported in with unknown function. However, tuzin is not characterized in parasites. In this study, we for the first time demonstrated that tuzin protein was expressed in both stages (promastigote and amastigote) of parasites. studies revealed that tuzin has potent antigenic properties. Therefore, we analyzed the immunogenicity of tuzin protein and immune response in BALB/c mice challenged with the parasite. We observed that tuzin-vaccinated mice have significantly reduced parasite burden in the spleen and liver compared with the control. The number of granulomas in the liver was also significantly decreased compared with the control groups. We further measured the IgG2a antibody level, a marker of Th1 immune response in VL, which was significantly higher in the serum of immunized mice when compared with the control. Splenocytes stimulated with soluble antigen (SLA) displayed a significant increase in NO and ROS levels compared with the control groups. Tuzin-immunized and parasite-challenged mice exhibit a notable rise in the IFN-γ/IL-10 ratio by significantly suppressing IL-10 expression level, an immunosuppressive cytokine that inhibits leishmanicidal immune function and encourages disease progression. In conclusion, tuzin immunizations substantially increase the protective immune response in -challenged mice groups compared with control.
内脏利什曼病(VL)被认为是最严重且致命的利什曼病类型,主要由 和 引起。预防该疾病传播的最有效方法是接种疫苗。直到如今,仍没有获批用于人类VL的有前景的疫苗。因此,有必要开展疫苗研究以丰富对抗利什曼病的治疗方法。Tuzin是一种罕见的跨膜蛋白,已在 中被报道但功能未知。然而,Tuzin在 寄生虫中尚未得到表征。在本研究中,我们首次证明Tuzin蛋白在 寄生虫的两个阶段(前鞭毛体和无鞭毛体)均有表达。 研究表明Tuzin具有强大的抗原特性。因此,我们分析了Tuzin蛋白的免疫原性以及在受到 寄生虫攻击的BALB/c小鼠中的免疫反应。我们观察到,与对照组相比,接种Tuzin的小鼠脾脏和肝脏中的寄生虫负荷显著降低。与对照组相比,肝脏中的肉芽肿数量也显著减少。我们进一步测量了IgG2a抗体水平,这是VL中Th1免疫反应的标志物,与对照组相比,免疫小鼠血清中的该抗体水平显著更高。与对照组相比,用可溶性 抗原(SLA)刺激的脾细胞中NO和ROS水平显著升高。接种Tuzin并受到寄生虫攻击的小鼠通过显著抑制IL-10表达水平,使IFN-γ/IL-10比值显著升高,IL-10是一种抑制利什曼杀伤免疫功能并促进疾病进展的免疫抑制细胞因子。总之,与对照组相比,接种Tuzin可显著增强受到 -攻击的小鼠组的保护性免疫反应。