The MASP family of Trypanosoma cruzi: changes in gene expression and antigenic profile during the acute phase of experimental infection.
The MASP family of Trypanosoma cruzi: changes in gene expression and antigenic profile during the acute phase of experimental infection.
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DOI：
10.1371/journal.pntd.0001779
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发表时间：
2012
影响因子：
3.8
通讯作者：
Bartholomeu DC
中科院分区：
文献类型：
--
作者：
dos Santos SL;Freitas LM;Lobo FP;Rodrigues-Luiz GF;Mendes TA;Oliveira AC;Andrade LO;Chiari E;Gazzinelli RT;Teixeira SM;Fujiwara RT;Bartholomeu DC
克氏锥虫是南美锥虫病的病原体，南美锥虫病是一种使人衰弱的疾病，影响着美洲数百万人。T. cruzi基因组计划发现了一个新的多基因家族，该家族由大约1,300个编码粘蛋白相关表面蛋白（MASPs）的基因组成。与其在寄生虫感染形式表面的定位相关的MASP家族的高水平多态性表明MASP参与宿主-寄生虫相互作用。我们推测MASP序列的大库可能有助于T. cruzi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7个cDNA文库进行测序，我们分析了MASP在来自不同宿主细胞的锥虫鞭毛体中的表达谱，并在急性感染小鼠中连续传代后进行了分析。此外，为了研究MASP抗原谱，我们对MASP蛋白进行了B细胞表位预测，并设计了具有110个推定表位的MASP特异性肽阵列，其用来自急性感染小鼠的血清筛选。我们观察到几个MASP基因之间的差异表达锥鞭毛体来源于上皮细胞和成肌细胞系。在急性感染小鼠中，在血流和组织培养锥鞭毛体之间以及在连续传代的血流形式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T。克氏感染，并构成由IgG和IgM抗体识别的寄生虫抗原。我们还发现，不同的MASP肽可以引发不同的抗体应答，并且针对给定肽的抗体水平可以在小鼠中连续传代后变化。我们推测，在感染期间MASP抗原肽的大库的变化可能有助于在恰加斯病的急性期期间逃避宿主免疫应答。寄生虫克氏锥虫是查加斯病的病原体，查加斯病是一种被忽视的热带疾病。T. cruzi基因组计划发现了一个编码粘蛋白相关表面蛋白（MASP）的多基因家族，该家族是在寄生虫感染形式的表面表达的高度多态性家族。我们推测MASP可能有助于T. cruzi感染几种宿主细胞和/或参与宿主免疫逃避机制。为了开始研究这一假设，我们分析了在小鼠中连续传代后在源自不同宿主细胞的锥虫鞭毛体和血流寄生虫中的MASP表达谱。我们还研究了急性感染小鼠中的MASP抗原谱。我们观察到更明显的MASP表达的变化，通过比较血流和组织培养锥鞭毛体之间的血流形式从感染的小鼠连续传代。我们还发现，MASP肽可引发不同的IgG和IgM抗体应答，并且针对给定肽的抗体水平在小鼠中连续传代后可变化。我们推测，在感染过程中MASP抗原肽的大库的变化可能有助于在恰加斯病的急性期逃避宿主免疫应答。
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. The parasite Trypanosoma cruzi is the etiologic agent of Chagas disease, a neglected tropical disease. A major finding of the T. cruzi genome project was the discovery of a multigene family that encodes mucin-associated surface proteins (MASP), a highly polymorphic family expressed at the surface of infective forms of the parasite. We speculate that MASP may contribute to the ability of T. cruzi to infect several host cells and/or participate in host immune evasion mechanisms. To begin investigating this hypothesis, we analyzed the MASP expression profile in trypomastigotes derived from different host cells and in bloodstream parasites after sequential passages in mice. We also investigated the MASP antigenic profile in acutely infected mice. We observed more pronounced MASP expression changes by comparing bloodstream and tissueculture trypomastigotes and between bloodstream forms from sequential passages in infected mice. We also found that MASP peptides could trigger different IgG and IgM 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 the course of an infection may contribute to the evasion of host immune responses during the acute phase of Chagas disease.
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影响因子：
3.1
作者：
Baida, RCP;Santos, WRM;da Silveira, JF
通讯作者：
da Silveira, JF
影响因子：
14.9
作者：
Bartholomeu, Daniella C.;Cerqueira, Gustavo C.;El-Sayed, Najib M.
通讯作者：
El-Sayed, Najib M.
DOI：
10.4269/ajtmh.2010.09-0399
发表时间：
2010-05-01
影响因子：
3.3
作者：
Adesse, Daniel;Iacobas, Dumitru A.;Spray, David C.
通讯作者：
Spray, David C.
影响因子：
6.4
作者：
Buscaglia, CA;Campetella, O;Frasch, ACC
通讯作者：
Frasch, ACC
DOI：
10.1590/s0074-02762010000600018
发表时间：
2010-09-01
期刊：
Memórias do Instituto Oswaldo Cruz
影响因子：
--
作者：
Andrade, Luciana O;Galvão, Lúcia MC;Macedo, Andrea M
通讯作者：
Macedo, Andrea M