Iborra Salvador, Parody Nuria, Abánades Daniel R, Bonay Pedro, Prates Deboraci, Novais Fernanda O, Barral-Netto Manoel, Alonso Carlos, Soto Manuel
Unidad de Inmunología Viral, Centro Nacional de Microbiología, Instituto de Salud Carlos III, Crta. Pozuelo Km 2, 28220 Majadahonda, Madrid, Spain.
Microbes Infect. 2008 Aug-Sep;10(10-11):1133-41. doi: 10.1016/j.micinf.2008.06.002. Epub 2008 Jun 17.
In the present work we analyze the antigenicity of Leishmania major ribosomal proteins (LRP) in infected BALB/c mice. We show that BALB/c mice vaccinated with LRP in the presence of CpG oligodeoxynucleotides (CpG-ODN) were protected against the development of dermal pathology and showed a reduction in the parasite load after challenge with L. major. This protection was associated with the induction of an IL-12 dependent specific-IFN-gamma response mediated mainly by CD4(+) T cell, albeit a minor contribution of CD8(+) T cells cannot be ruled out. Induction of Th1 responses against LRP also resulted in a reversion of the Th2 responses associated with susceptibility. A marked reduction of IgG1 antibody titer against parasite antigens besides an impaired IL-4 and IL-10 cytokine production by parasite specific T cells was observed. In addition, we show that the administration of the LRP plus CpG-ODN preparation also conferred protection in the naturally resistant C57BL/6 mice. In this strain protection was associated with a LRP specific IFN-gamma production in lymph nodes draining the challenge site. We believe that these evolutionary conserved proteins, combined with adjuvants that favor Th1 responses, may be relevant components of a pan-Leishmania vaccine.
在本研究中,我们分析了感染利什曼原虫的BALB/c小鼠中硕大利什曼原虫核糖体蛋白(LRP)的抗原性。我们发现,在CpG寡脱氧核苷酸(CpG-ODN)存在的情况下用LRP免疫的BALB/c小鼠可免受皮肤病理发展的影响,并且在用硕大利什曼原虫攻击后寄生虫负荷降低。这种保护作用与主要由CD4(+) T细胞介导的IL-12依赖性特异性IFN-γ反应的诱导有关,尽管不能排除CD8(+) T细胞的轻微贡献。针对LRP的Th1反应的诱导也导致了与易感性相关的Th2反应的逆转。除了寄生虫特异性T细胞产生的IL-4和IL-10细胞因子受损外,还观察到针对寄生虫抗原的IgG1抗体滴度显著降低。此外,我们表明,LRP加CpG-ODN制剂的给药也能使天然抗性的C57BL/6小鼠获得保护。在该品系中,保护作用与攻击部位引流淋巴结中LRP特异性IFN-γ的产生有关。我们认为,这些进化保守的蛋白质与有利于Th1反应的佐剂相结合,可能是泛利什曼原虫疫苗的相关成分。