Departamento de Parasitologia, Universidade Federal de Minas Gerais, Minas Gerais, Brazil.
PLoS Negl Trop Dis. 2012;6(8):e1779. doi: 10.1371/journal.pntd.0001779. Epub 2012 Aug 14.
Trypanosoma cruzi is the etiological agent of Chagas disease, a debilitating illness that affects millions of people in the Americas. A major finding of the T. cruzi genome project was the discovery of a novel multigene family composed of approximately 1,300 genes that encode mucin-associated surface proteins (MASPs). The high level of polymorphism of the MASP family associated with its localization at the surface of infective forms of the parasite suggests that MASP participates in host-parasite interactions. We speculate that the large repertoire of MASP sequences may contribute to the ability of T. cruzi to infect several host cell types and/or participate in host immune evasion mechanisms.
By sequencing seven cDNA libraries, we analyzed the MASP expression profile in trypomastigotes derived from distinct host cells and after sequential passages in acutely infected mice. Additionally, to investigate the MASP antigenic profile, we performed B-cell epitope prediction on MASP proteins and designed a MASP-specific peptide array with 110 putative epitopes, which was screened with sera from acutely infected mice.
We observed differential expression of a few MASP genes between trypomastigotes derived from epithelial and myoblast cell lines. The more pronounced MASP expression changes were observed between bloodstream and tissue-culture trypomastigotes and between bloodstream forms from sequential passages in acutely infected mice. Moreover, we demonstrated that different MASP members were expressed during the acute T. cruzi infection and constitute parasite antigens that are recognized by IgG and IgM antibodies. We also found that distinct MASP peptides could trigger different antibody responses and that the antibody level against a given peptide may vary after sequential passages in mice. We speculate that changes in the large repertoire of MASP antigenic peptides during an infection may contribute to the evasion of host immune responses during the acute phase of Chagas disease.
克氏锥虫是恰加斯病的病原体，这种使人虚弱的疾病影响着美洲数百万人。克氏锥虫基因组计划的一个主要发现是发现了一个由大约 1300 个基因组成的新型多基因家族，这些基因编码粘蛋白相关表面蛋白（MASP）。MASP 家族的高度多态性与其定位于寄生虫感染形式的表面有关，这表明 MASP 参与了宿主-寄生虫的相互作用。我们推测，大量的 MASP 序列可能有助于克氏锥虫感染几种宿主细胞类型和/或参与宿主免疫逃避机制。
通过对七个 cDNA 文库进行测序，我们分析了源自不同宿主细胞的、在急性感染小鼠中连续传代后的锥虫动质体中的 MASP 表达谱。此外，为了研究 MASP 抗原表位，我们对 MASP 蛋白进行了 B 细胞表位预测，并设计了一个含有 110 个潜在表位的 MASP 特异性肽阵列，用急性感染小鼠的血清进行了筛选。
我们观察到源自上皮细胞系和肌母细胞系的锥虫动质体之间有几个 MASP 基因的差异表达。在血液期和组织培养期锥虫动质体之间，以及在急性感染小鼠连续传代的血液期锥虫动质体之间，观察到更明显的 MASP 表达变化。此外，我们证明了不同的 MASP 成员在急性克氏锥虫感染期间表达，并构成了被 IgG 和 IgM 抗体识别的寄生虫抗原。我们还发现，不同的 MASP 肽段可以触发不同的抗体反应，并且针对给定肽段的抗体水平在小鼠连续传代后可能会发生变化。我们推测，在感染过程中大量的 MASP 抗原肽的变化可能有助于在恰加斯病的急性阶段逃避宿主的免疫反应。
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