Das Pranati, Amit Ajay, Singh Shubhankar Kumar, Chaudhary Rajesh, Dikhit Manas Ranjan, Yadav Anupam, Pandey Krishna, Das Vidya Nand Rabi, Sundram Shanty, Das P, Bimal Sanjiva
Division of Immunology, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, 800007India.
Department of Biomedical Informatics, Rajendra Memorial Research Institute of Medical Sciences, Agamkuan, Patna, Bihar, 800007India.
Parasitol Int. 2015 Feb;64(1):18-25. doi: 10.1016/j.parint.2014.08.004. Epub 2014 Sep 16.
As phospho proteins are reported to be involved in virulence and survival, the ability of Leishmania to inhibit macrophage effector functions may result from a direct interference of leishmanial molecules with macrophage signal transduction pathways. Several such proteins such as pp63, pp41 and pp29 have also been identified as a Th1 stimulatory protein in the Leishmania donovani. In the present study, the immunogenicity of a cocktail of pp63+pp41+pp29 was assessed by estimation of serum antibody titre, nitric oxide(NO) production, estimation of Th1 cytokine(IFN-γ) as well as Th2 cytokines(IL-4), and determination of parasite load in L. donovani infected mice. In the group immunized with antigenic cocktail there was a sharp rise in antibody titer up to Day 20 which reduced considerably by Day 50. Groups of mice vaccinated with pp63, pp41, pp29 and the antigenic cocktail expressed 10-fold, 16-fold, 22-fold and 25-fold increase respectively in NO production by splenocytes. The animal groups immunized with pp63, pp41, pp29 and the antigenic cocktail showed reduced parasite load in the liver and spleen, as well as increased IFN-gamma production in the spleen. Furthermore immunized animals remained with a normal hematological profile, whereas L. donovani in unimmunized mice lead to significant anemia.
由于据报道磷酸化蛋白参与了毒力和生存过程,利什曼原虫抑制巨噬细胞效应功能的能力可能源于利什曼原虫分子对巨噬细胞信号转导途径的直接干扰。几种这样的蛋白,如pp63、pp41和pp29,也已被鉴定为杜氏利什曼原虫中的一种Th1刺激蛋白。在本研究中,通过估计血清抗体滴度、一氧化氮(NO)产生量、Th1细胞因子(IFN-γ)以及Th2细胞因子(IL-4)的水平,并测定杜氏利什曼原虫感染小鼠体内的寄生虫载量,评估了pp63+pp41+pp29混合物的免疫原性。在用抗原混合物免疫的组中,抗体滴度在第20天之前急剧上升,到第50天时大幅下降。用pp63、pp41、pp29和抗原混合物接种疫苗的小鼠组,脾细胞产生的NO分别增加了10倍、16倍、22倍和25倍。用pp63、pp41、pp29和抗原混合物免疫的动物组,肝脏和脾脏中的寄生虫载量降低,脾脏中IFN-γ的产生增加。此外,免疫动物的血液学指标保持正常,而未免疫小鼠体内的杜氏利什曼原虫导致了明显的贫血。