Carrillo E, Ahmed S, Goldsmith-Pestana K, Nieto J, Osorio Y, Travi B, Moreno J, McMahon-Pratt D
WHO Collaborating Centre for Leishmaniasis, Instituto de Salud Carlos III, Ctra. Majadahonda-Pozuelo km. 2, 28220 Madrid, Spain.
Vaccine. 2007 Feb 9;25(8):1534-43. doi: 10.1016/j.vaccine.2006.10.036. Epub 2006 Nov 10.
The P-8 proteoglycolipid complex (P-8 PGLC), an amastigote antigen of Leishmania pifanoi, has been demonstrated to induce protection in mouse models, as well as to induce Tc1/Th1-like cellular responses in American cutaneous leishmaniasis patients. Because the immunization with P-8 PGLC in the murine model does not appear to be genetically restricted, we have studied the reactivity of the P-8 PGLC in Leishmania infantum infected dogs. In this study, it is shown that PBMC from experimentally infected dogs (asymptomatic, oligosymptomatic) significantly proliferated in response to soluble leishmanial antigen (SLA) or the P-8 PGLC. Further, quantification of the gene expression induced by the stimulation with P-8 in asymptomatically infected dogs showed an up-regulation of IFN-gamma and TNF-alpha, which were three to 4-fold higher than that induced by soluble Leishmania antigen (SLA). While no measurable induction of IL-10 was observed, low levels of IL-4 mRNA were observed in response to both P-8 and SLA antigens. Thus, our studies establish that P-8 is recognized by infected canines and elicits a potentially curative/protective Th1-like immune response. The identification of Leishmania antigens that elicit appropriate immune responses across different host species (humans, canine) and disease manifestations (cutaneous or visceral) could be an advantage in generating a general vaccine for leishmaniasis.
P-8蛋白糖脂复合物(P-8 PGLC)是皮氏利什曼原虫无鞭毛体抗原,已证实在小鼠模型中可诱导产生保护作用,并且在美国皮肤利什曼病患者中可诱导产生Tc1/Th1样细胞反应。由于在鼠模型中用P-8 PGLC免疫似乎不受基因限制,我们研究了P-8 PGLC在婴儿利什曼原虫感染犬中的反应性。在本研究中,结果显示,来自实验感染犬(无症状、症状轻微)的外周血单核细胞(PBMC)对可溶性利什曼原虫抗原(SLA)或P-8 PGLC有显著增殖反应。此外,对无症状感染犬用P-8刺激诱导的基因表达进行定量分析,结果显示干扰素-γ(IFN-γ)和肿瘤坏死因子-α(TNF-α)上调,其水平比可溶性利什曼原虫抗原(SLA)诱导的水平高3至4倍。虽然未观察到白细胞介素-10(IL-10)的可测量诱导,但对P-8和SLA抗原均观察到低水平的白细胞介素-4(IL-4)mRNA。因此,我们的研究证实感染犬可识别P-8,并引发潜在的治愈性/保护性Th1样免疫反应。鉴定能在不同宿主物种(人类、犬)和疾病表现(皮肤或内脏)中引发适当免疫反应的利什曼原虫抗原,可能有助于开发一种通用的利什曼病疫苗。