Teixeira Priscila Camillo, Velasquez Leonardo Garcia, Lepique Ana Paula, de Rezende Eloiza, Bonatto José Matheus Camargo, Barcinski Marcello Andre, Cunha-Neto Edecio, Stolf Beatriz Simonsen
Heart Institute (InCor), University of São Paulo School of Medicine, São Paulo, São Paulo, Brazil.
Department of Parasitology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
PLoS Negl Trop Dis. 2015 Feb 18;9(2):e0003411. doi: 10.1371/journal.pntd.0003411. eCollection 2015 Feb.
Leishmaniasis is an important disease that affects 12 million people in 88 countries, with 2 million new cases every year. Leishmania amazonensis is an important agent in Brazil, leading to clinical forms varying from localized (LCL) to diffuse cutaneous leishmaniasis (DCL). One interesting issue rarely analyzed is how host immune response affects Leishmania phenotype and virulence. Aiming to study the effect of host immune system on Leishmania proteins we compared proteomes of amastigotes isolated from BALB/c and BALB/c nude mice. The athymic nude mice may resemble patients with diffuse cutaneous leishmaniasis, considered T-cell hyposensitive or anergic to Leishmania's antigens. This work is the first to compare modifications in amastigotes' proteomes driven by host immune response. Among the 44 differentially expressed spots, there were proteins related to oxidative/nitrosative stress and proteases. Some correspond to known Leishmania virulence factors such as OPB and tryparedoxin peroxidase. Specific isoforms of these two proteins were increased in parasites from nude mice, suggesting that T cells probably restrain their posttranslational modifications in BALB/c mice. On the other hand, an isoform of HSP70 was increased in amastigotes from BALB/c mice. We believe our study may allow identification of potential virulence factors and ways of regulating their expression.
利什曼病是一种重要疾病,在88个国家影响着1200万人,每年有200万新病例。亚马逊利什曼原虫是巴西的一种重要病原体,可导致从局限性皮肤利什曼病(LCL)到弥漫性皮肤利什曼病(DCL)等不同临床类型。一个很少被分析的有趣问题是宿主免疫反应如何影响利什曼原虫的表型和毒力。为了研究宿主免疫系统对利什曼原虫蛋白质的影响,我们比较了从BALB/c和BALB/c裸鼠分离的无鞭毛体的蛋白质组。无胸腺裸鼠可能类似于弥漫性皮肤利什曼病患者,被认为对利什曼原虫抗原的T细胞反应低下或无反应。这项工作首次比较了由宿主免疫反应驱动的无鞭毛体蛋白质组的变化。在44个差异表达斑点中,有与氧化/亚硝化应激和蛋白酶相关的蛋白质。一些对应于已知的利什曼原虫毒力因子,如OPB和锥虫过氧化物酶。这两种蛋白质的特定异构体在裸鼠的寄生虫中增加,表明T细胞可能在BALB/c小鼠中抑制它们的翻译后修饰。另一方面,HSP70的一种异构体在BALB/c小鼠的无鞭毛体中增加。我们相信我们的研究可能有助于识别潜在的毒力因子及其表达调控方式。