Mapping the Antigenicity of the Parasites in Leishmania donovani Infection by Proteome Serology
Mapping the Antigenicity of the Parasites in Leishmania donovani Infection by Proteome Serology
复制标题
DOI：
10.1371/journal.pone.0000040
复制
发表时间：
2006-12-20
期刊：
影响因子：
3.7
通讯作者：
Walden, Peter
中科院分区：
文献类型：
--
作者：
Forgber, Michael;Basu, Rajatava;Walden, Peter
背景利什曼病定义了一组具有不同临床表现的原虫病。由杜氏利什曼原虫引起的内脏型是最严重的。到目前为止，尽管有迹象表明内脏利什曼病可以自然产生免疫力，但还没有针对内脏利什曼病的疫苗，而且敏感的免疫诊断学仍处于早期开发阶段。方法/主要结论。建立蛋白质组-血清学方法，我们绘制了寄生虫的抗原性和特异性的免疫反应在人类利什曼病。使用二维蛋白质印迹分析从印度患者分离的血清和寄生虫，我们检测到免疫反应与广泛不同的特异性高达330种不同的利什曼原虫抗原。在银和荧光染料染色的凝胶中，68种抗原被指定为蛋白质。这些蛋白的抗原性与蛋白的表达水平无关。虽然不同的寄生虫分离株之间有一些共同的抗原，但存在广泛的差异，没有免疫显性抗原，但表明寄生虫中的抗原漂移。通过质谱鉴定了6种抗原。结论/意义。基于蛋白质组学的解剖利什曼病患者的血清特异性提供了一个全面的库存的复杂性和个体间异质性的主机响应和变化的利什曼原虫寄生虫的抗原性。这些信息可以帮助开发疫苗和新的免疫监测和诊断设备。
Background. Leishmaniasis defines a cluster of protozoal diseases with diverse clinical manifestations. The visceral form caused by Leishmania donovani is the most severe. So far, no vaccines exist for visceral leishmaniasis despite indications of naturally developing immunity, and sensitive immunodiagnostics are still at early stages of development. Methodology/Principle Findings. Establishing a proteome-serological methodology, we mapped the antigenicity of the parasites and the specificities of the immune responses in human leishmaniasis. Using 2-dimensional Western blot analyses with sera and parasites isolated from patients in India, we detected immune responses with widely divergent specificities for up to 330 different leishmanial antigens. 68 antigens were assigned to proteins in silver- and fluorochrome-stained gels. The antigenicity of these proteins did not correlate with the expression levels of the proteins. Although some antigens are shared among different parasite isolates, there are extensive differences and no immunodominant antigens, but indications of antigenic drift in the parasites. Six antigens were identified by mass spectrometry. Conclusions/Significance. Proteomics-based dissection of the serospecificities of leishmaniasis patients provides a comprehensive inventory of the complexity and interindividual heterogeneity of the host-responses to and variations in the antigenicity of the Leishmania parasites. This information can be instrumental in the development of vaccines and new immune monitoring and diagnostic devices.