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Immunogenicity of the P-8 amastigote antigen in the experimental model of canine visceral leishmaniasis

机译:P-8鞭毛鞭毛虫抗原在犬内脏利什曼病实验模型中的免疫原性

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摘要

The P-8 proteoglycolipid complex (P-8 PGLC), an amastigote antigen of L. 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 L. 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-γ and TNF-α, which were three to four-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.
机译:已证明P-8蛋白糖脂复合物(P-8 PGLC)是pifanoi的鞭毛体抗原,可在小鼠模型中诱导保护作用,并在美国皮肤利什曼病患者中诱导类似Tc1 / Th1的细胞反应。因为在鼠模型中用P-8 PGLC进行的免疫似乎没有遗传上的限制,所以我们研究了P-8 PGLC在被婴儿乳杆菌感染的狗中的反应性。在这项研究中,表明来自实验感染狗(无症状,有症状)的PBMC响应可溶性利什曼原虫抗原(SLA)或P-8 PGLC明显增生。此外,对无症状感染的狗中P-8刺激诱导的基因表达进行定量显示,IFN-γ和TNF-α上调,比可溶性利什曼原虫抗原(SLA)诱导的上调三到四倍。 )。虽然未观察到可测量的IL-10诱导,但观察到对P-8和SLA抗原均应答的IL-4 mRNA水平低。因此,我们的研究确定P-8被感染的犬类识别并引发潜在的治愈性/保护性Th1样免疫应答。利什曼原虫抗原的鉴定可在不同宿主物种(人,犬)和疾病表现形式(皮肤或内脏)之间引发适当的免疫反应,这可能是产生利什曼原虫病通用疫苗的一个优势。

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